Structural-functional organisation of the bone marrow hematopoietic stem cells niches

Home/2016, Vol. 4, No. 1/Structural-functional organisation of the bone marrow hematopoietic stem cells niches

Cell and Organ Transplantology. 2016; 4(1):100-117.
DOI: 10.22494/COT.V4I1.9

Structural-functional organisation of the bone marrow hematopoietic stem cells niches

Nikolskaya E. I., Butenko G. M.
State Institute of Genetic and Regenerative Medicine NAMS of Ukraine, Kyiv, Ukraine

 Abstract
This article focuses on (1) the analysis of the structural-functional organization of bone marrow niches of the hematopoietic stem cells, (2) the role of the intercellular contact interactions and humoral regulation factors in these niches, in particular CXCL12, SCF and TGFβ, and (3) the intracellular signal pathways: Notch, Wnt and Shh. The two types of niches, switching from one into another: endosteal niches located on the endost surface at the borderline with bone marrow cavity and the vascular niches included into bone marrow parenchyma. It is emphasized that the main role in the formation of the niches of both types is ascribed to the multipotent stromal cells, which serve as a base for differentiation of the osteoblasts, spindle-shaped N-cadherin+CD45 osteoblasts (SNO-cells), nestin-expressing cells (Nes+ cells), cells with leptin receptor (Lepr+ cells), abundant producing CXCL12 reticular cells (CAR-cells) and NG2-pericytes. The endothelial cells are no less important. Also, the adipocytes, osteoclasts, macrophages and megakaryocytes, regulatory T-cells and neuronal cells are involved in the niche functioning. It is postulated that osteoblasts and CAR-cells play a crucial role in the genesis of immune system cells: common lymphoid precursors, B-lymphocytes, natural killer and dendritic cells.

Key words: bone marrow, hematopoietic stem cell niche, multipotent stromal cells, hematopoiesis

Full Text PDF (eng) Full Text PDF (ua)

1. Chertkov IL, Gurevich OA. Stvolovaya krovetvornaya kletka i ee mikrookruzhenie [Stem cells and their microenvironment]. Moscow: Meditsina, 1984, 240 p. [in Russian].
2. Howe RJ, Howe MA, Tankovich NI, et al. The Miracle of Stem Cells: How Adult Stem Cells Are Transforming Medicine Hardcover. Rancho Santa Fe: Stemeddica Cell Technologies, 2011. 282 p.
3. Bond VP, Fliedner ТМ, Archambeau JO. Mammalian radiation lethality. New York: Acad. Press, 1965. 320 p.
4. Ivanova NB, Dimos JT, Schaniel C, et al. A stem cell molecular signature. Science. 2002; 298(5593): 601-4. https://doi.org/10.1126/science.1073823   PMid:12228721
5. Ramalho-Santos M, Yoon S, Matsuzaki Y, et al. “Stemness”: transcriptional profiling of embryonic and adult stem cells. Science. 2002; 298(5593): 597-600. https://doi.org/10.1126/science.1072530  PMid:12228720
6. Ema H, Sudo K, Seita J, et al. Quantification of self-renewal capacity in single hematopoietic stem cells from normal and Lnk-deficient mice. Dev Cell. 2005; 8(6): 907-14.https://doi.org/10.1016/j.devcel.2005.03.019   PMid:15935779
7. Kiel MJ, Yilmaz OH, Iwashita T, et al. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell. 2005; 121(7): 1109–21.https://doi.org/10.1016/j.cell.2005.05.026   PMid:15989959
8. Kiel MJ, Yilmaz OH, Morrison SJ. CD150-cells are transiently reconstituting multipotent progenitors with little or no stem cell activity. Blood. 2008; 111(8): 4413-14. https://doi.org/10.1182/blood-2007-12-129601   PMid:18398056      PMCid:PMC2293285
9. Morita Y, Ema H, Nakauchi H. Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment. J Exp Med. 2010; 207(6): 1173-82. https://doi.org/10.1084/jem.20091318  PMid:20421392      PMCid:PMC2882827
10. Petzer AL, Hogge DE, Landsdorp PM, et al. Self-renewal of primitive human hematopoietic cells (long-term-culture-initiating cells) in vitro and their expansion in defined medium. Proc Natl Acad Sci USA. 1996; 93(4): 1470-74. https://doi.org/10.1073/pnas.93.4.1470   PMid:8643656      PMCid:PMC39963
11. Bradford GB, Williams B, Rossi R, et al. Quiescence, cycling, and turnover in the primitive hematopoietic stem cell compartment. Exp Hematol. 1997; 25(5): 445-53.
12. Cheshier SH, Morrison SJ, Liao X, et al. In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells. Proc Natl Acad Sci USA. 1999; 96(6): 3120-25.https://doi.org/10.1073/pnas.96.6.3120   PMid:10077647      PMCid:PMC15905
13. Sudo K, Ema H, Morita Y, et al. Age-associated characteristics of murine hematopoietic stem cells. J Exp Med. 2000; 192(9): 1273-80. https://doi.org/10.1084/jem.192.9.1273   PMid:11067876      PMCid:PMC2193349
14. Wilson A, Laurenti E, Oser G, et al. Hematopoietic stem cells reversibly switch from dormancy to self-renewal during homeostasis and repair. Cell. 2008; 135(6): 1118-29.https://doi.org/10.1016/j.cell.2008.10.048   PMid:19062086
15. Morita Y, Iseki A, Okamura S, et al. Functional characterization of hematopoietic stem cells in the spleen. Exp Hematol. 2011; 39(3): 351-59. https://doi.org/10.1016/j.exphem.2010.12.008  PMid:21185906
16. Brown G, Mooney CJ, Alberti-Servera L, et al. Versatility of stem and progenitor cells and the instructive actions of cytokines on hematopoiesis. Crit Rev Clin Lab Sci. 2015; 52(4): 168-79.
17. Magli МС, Iscove NN, Odartchenko N. Transient nature of early haemopoietic spleen colonies. Nature. 1982; 295(5849): 527-29. https://doi.org/10.1038/295527a0
18. Dexter TM. Gemopoeticheskie rostovye faktory: biologicheskie effekty i perspektivy klinicheskogo primeneniya [Hematopoietic growth factors: biological effects and perspectives of clinical applications]. Ontogenez – Ontogenesis. 1991; 22(4): 341-64 [in Russian].
19. Mendes SC, Robin C, Dzierzak E. Mesenchymal progenitor cells localize within hematopoietic sites throughout ontogeny. Development. 2005; 132(5): 1127-36. https://doi.org/10.1242/dev.01615  PMid:15689383
20. Al-Drees MA, Yeo JH, Boumelhem BB, et al. Making Blood: The Haematopoietic Niche throughout Ontogeny. Stem Cells Int. 2015; 2015. Available: Available: http://dx.doi.org/10.1155/2015/571893.https://doi.org/10.1155/2015/571893
21. Tavassoli М, Maniatis A, Crosby WH. Induction of sustained hematopoiesis in fatty marrow. Blood. 1974; 43(1): 33-8.
22. Cumano A, Godin I. Ontogeny of the hematopoietic system. Annu Rev Immunol. 2007; 25: 745-85. https://doi.org/10.1146/annurev.immunol.25.022106.141538   PMid:17201678
23. Orkin SH, Zon Orkin LI. SnapShot: hematopoiesis. Cell. 2008; 132(4): 712.
24. Kricun ME. Red-yellow marrow conversion: its effect on the location of some solitary bone lesions. Skeletal Radiol. 1985; 14(1): 10-19. https://doi.org/10.1007/BF00361188   PMid:3895447
25. O’Malley DP, Kim YS, Perkins SL, et al. Morphologic and immunohistochemical evaluation of splenic hematopoietic proliferations in neoplastic and benign disorders. Mod Pathol. 2005; 18(12): 1550-61. https://doi.org/10.1038/modpathol.3800480
26. Weiss L. A scanning electron microscopic study of the spleen. Blood. 1974; 43(5): 665-91.
27. Kostyushev DS, Simirsky VN, Song S, et al. Stvolovye kletki i mikrookruzhenie: integratsiya biokhimicheskikh i mekhanicheskikh faktorov [Stem cells and the microenvironment: the integration of biological and mechanical factors]. Uspekhi sovremennoy biologii – Biology Bulletin Reviews. 2014; 134(1): 3-18 [in Russian].
28. Payushina OV. Krovetvornoe mikrookruzhenie i rol’ mezenkhimnykh stromal’nykh kletok v ego organizatsii [Hematopoietic microenvironment and the role of mesenchymal stromal cells in his organization]. Uspekhi sovremennoy biologii – Biology Bulletin Reviews. 2015; 135(1): 52-63 [in Russian].
29. Goodell M. Introduction to a review series on hematopoietic stem cells. Blood. 2015; 125(17): 2587. https://doi.org/10.1182/blood-2015-03-615005   PMid:25762178
30. Friedenstein AJ, Chailakhyan RK, Latsinik NV, et al. Stromal’nye kletki, otvetstvennye za perenos mikrookruzheniya v krovetvornoy i limfoidnoy tkani [Stromal cells responsible for transferring the microenvironment in hematopoietic and lymphoid tissue]. Probl. Gematol. – Problems of Hematology. 1973; 10: 14-23 [in Russian].
31. Wolf NS, Trentin JJ. Hematopoietic colony studies. V. Effect of hematopoietic organ stroma on differentiation of pluripotent stem cells. J Exp Med. 1968; 127(1): 205-14.https://doi.org/10.1084/jem.127.1.205
32. Chertkov IL, Gurevich OA, Udalov GA. Izuchenie kletok, perenosyashchikh krovetvornoe mikrookruzhenie, s pomoshch’yu geterotopnoy transplantatsii kostnogo mozga [Studying of cells undergoing hematopoietic microenvironment by heterotopic transplantation of bone marrow]. Rol’ stvolovyh kletok v lejkozo- i kancerogeneze – The role of stem cells in the leukosis- and carcinomagenesis. Kiev, 1977; pp. 16-18 [in Russian].
33. Amsel S, Maniatis A, Tavassoli М, et al. The significance of intramedullary cancellous bone formation in the repair of bone marrow tissue. Anat Rec. 1969; 164(1): 101-11.https://doi.org/10.1002/ar.1091640107   PMid:5769818
34. Knospe WH, Gregory SA, Fried W, et al. Stimulation of hematopoiesis by femoral marrow curettage in sublethally irradiated mice. Blood. 1973; 41(4): 519-27.
35. Mawdsley R, Harrison GA. Fate of transplanted bone. Nature. 1963; 198(4879): 495-96. https://doi.org/10.1038/198495a0
36. Friedenstein AJ, Ivanov-Smolenski AA, Chajlakjan RK, et al. Origin of bone marrow stromal mechanocytes in radiochimeras and heterotopic transplants. Exp Hematol. 1978; 6(5): 440-44.
37. Chui DHK, Russel ES. Fetal erythropoiesis in steel mutantmice. I. A morphological study of erythroid cell development in fetal liver. Developm Biol. 1974; 40(2): 256-69.
38. Kitamura Y, Go S. Decreased production of mast cells in SlSld anemic mice. Blood. 1979; 53(3): 492-97.
39. Altus MS, Bernstein SE, Russel ES, et al. Defect extrinsic to stem cells in spleens of steel anemic mice. Proc Soc exp Biol Med (N. Y.). 1971; 138(3): 985-88.
40. Wolf NS. Dissecting the hematopoietic microenvironment. II. The kinetics of the erythron of the Sl Sld mouse and the dual nature of its anemia. Cell Tiss Kinet. 1978; 11(4): 325-34.
41. Schofield R. The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells. 1978; 4(1-2): 7-25.
42. Samoilina NL. Proliferativnaya aktivnost’ stvolovykh krovetvornykh «letok v dlitel’nykh organotipicheskikh kul’turakh embrional’noy pecheni myshey [The proliferative activity of hematopoietic stem cells into the long-term organotypic cultures of embryonic mouse liver]. Byull. eksper. Biol. – Bull. Exper. Biol. 1982; 7: 94-5 [in Russian].
43. Dexter ТМ, Moore MAS, Sheridan APC. Maintenance of hematopoietic stem cells and production of differentiated progeny in allogeneic and se- miallogeneic bone marrow chimeras in vitro. J exp Med. 1977; 145(6): 1612-16. https://doi.org/10.1084/jem.145.6.1612
44. Moore MA, Sheridan AP, Allen TD, et al. Prolonged hematopoiesis in a primate bone marrow culture system: characteristics of stem cell production and the hematopoietic microenvironment. Blood. 1979; 54(4): 775-93.
45. Friedenstein AJ, Luria EA. Kletochnye osnovy krovetvornogo mikrookruzheniya [Cell basics of hematopoietic microenvironment]. Moscow: Medicine, 1980, 216 p. [in Russian].
46. Bentley SA, Foidart JM. Some properties of marrow derived adherent cells in tissue culture. Blood. 1980; 56(6): 1006-12.
47. Bentley SA. Close range cell: cell interaction required stem cell mainte¬nance in continuous bone marrow culture. Exp Hematol. 1981; 9(3): 308-12.
48. Blackburn MJ, Goldman JM. Increased haemopoietic cell survival in vitro induced by a human marrow fibroblast factor. Brit J Haemat. 1981; 48(1): 117-25.
49. Breems DA, Blokland EA, Siebel KE, et al. Stroma-contact prevents loss of hematopoietic stem cell quality during ex vivo expansion of CD34+ mobilized peripheral blood stem cells. Blood. 1998; 91(1): 111-17.
50. Majumdar MK, Thiede MA, Haynesworth SE, et al. Human marrow-derived mesenchymal stem cells (MSCs) express hematopoietic cytokines and support long-term hematopoiesis when differentiated toward stromal and osteogenic lineages. J Hematother Stem Cell Res. 2000; 9(6): 841-48. https://doi.org/10.1089/152581600750062264   PMid:11177595
51. Petevka NV, Goncharov NV, Kostyunina VS, et al. Ekspansiya krovetvornykh kletok pupovinnoy krovi cheloveka v usloviyakh sokul’tivirovaniya s mezenkhimnymi stromal’nymi kletkami kostnogo mozga [Expansion of human cord blood hematopoietic cells in a culture with a bone marrow mesenchymal stromal cells]. Zhurnal NAMN Ukraїni – Journal of NAMS of Ukraine. 2012; 18(Suppl.):120-21 [in Russian].
52. Kostyunina VS, Petevka NV, Goncharov NV, et al. Mezenkhimnye stromal’nye kletki pupovinno-platsentarnogo proiskhozhdeniya sposobstvuyut ekspansii gemopoeticheskikh CD34+-kletok pupovinnoy krovi cheloveka in vitro [Mesenchymal stromal cells of umbilical-placental origin contribute to the expansion of hematopoietic of CD34 + cells of human umbilical cord blood in vitro]. Zhurnal NAMN Ukraїni – Journal of NAMS of Ukraine. 2012; 18(suppl.): 74-5 [in Russian].
53. Wilson A, Trumpp A. Bone-marrow haematopoietic-stem-cell niches. Nature Reviews Immunology. 2006; 6(2): 93-106. https://doi.org/10.1038/nri1779   PMid:16491134
54. Alakel N, Jing D, Muller K, et al. Direct contact with mesenchymal stromal cells affects migratory behavior and gene expression profile of CD133+ hematopoietic stem cells during ex vivo expansion. Exp Hematol. 2009; 37(4): 504-13. https://doi.org/10.1016/j.exphem.2008.12.005   PMid:19216019
55. Uchida N, He D, Friera AM, et al. The unexpectedG0 G1 cell cycle status of mobilized hematopoietic stem cells from peripheral blood. Blood. 1997; 89(2): 465-72.
56. Heike T, Nakahata T. Ex vivo expansion of hematopoietic stem cells by cytokines. Biochim Biophys Acta. 2002; 1592(3): 313-21. https://doi.org/10.1016/S0167-4889(02)00324-5
57. Jing D, Fonseca AV, Alakel N, et al. Hematopoietic stem cells in co-culture with mesenchymal stromal cells–modeling the niche compartments in vitro. Haematologica. 2010; 95(4): 542-50.https://doi.org/10.3324/haematol.2009.010736   PMid:20145267      PMCid:PMC2857183
58. Sipkins DA, Wei X, Wu JW, et al. In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment. Nature. 2005; 435(7044): 969-73. https://doi.org/10.1038/nature03703  PMid:15959517      PMCid:PMC2570168
59. Nombela- C Arrieta, Pivarnik G, Winkel B, et al. Quantitative imaging of haematopoietic stem and progenitor cell localization and hypoxic status in the bone marrow microenvironment. Nat Cell Biol. 2013; 15(5): 533-43. https://doi.org/10.1038/ncb2730   PMid:23624405      PMCid:PMC4156024
60. Campbell F. Ultrastructural studies of transmural migration of blood cells in the bone marrow of rats, mice and guinea pigs. American Journal of Anatomy. 1972; 135(4): 521-36.https://doi.org/10.1002/aja.1001350406   PMid:4637868
61. Martin TJ, Sims NA. Osteoclast-derived activity in the coupling of bone formation to resorption Trends Mol Med. 2005; 11(2): 76–81.
62. Kollet O, Dar A, Shivtiel S, et al. Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells. Nature Medicine. 2006; 12(6): 657–64.https://doi.org/10.1038/nm1417   PMid:16715089
63. Zhang J, Niu C, Ye L, et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature. 2003; 425(6960): 836-41. https://doi.org/10.1038/nature02041   PMid:14574412
64. Nilsson SK, Debatis ME, Dooner MS, et al. Immunofluorescence characterization of key extracellular matrix proteins in murine bone marrow in situ. J Histochem Cytochem. 1998; 46(3): 371-77.https://doi.org/10.1177/002215549804600311   PMid:9487119
65. Aubin JE, Liu F, Malaval L, et al. Osteoblast and chondroblast differentiation. Bone. 1995; 17(Suppl. 2): 77S–83S.
66. Aubin JE. Advances in the osteoblast lineage. Biochem Cell Biol. 1998; 76(6): 899-910. https://doi.org/10.1139/o99-005   PMid:10392704
67. Cordeiro-Spinetti E, De-Mello W, Trindade LS, et al. Human bone marrow mesenchymal progenitors: perspectives on an optimized in vitro manipulation. Front Cell Dev Biol. 2014; 2. Available: http://dx.doi.org/10.3389/fcell.2014.00007 https://doi.org/10.3389/fcell.2014.00007
68. Matrosova VY, Orlovskaya IA, Serobyan N, et al. Hyaluronic acid facilitates the recovery of hematopoiesis following 5-fluorouracil administration. Stem Cells. 2004; 22(4): 544-55.https://doi.org/10.1634/stemcells.22-4-544   PMid:15277700
69. Goldberg ED, Dygai AM, Zyuz’kov GN, et al. Mekhanizmy mobilizatsii mezenkhimal’nykh kletok-predshestvennikov granulotsitarnym koloniestimuliruyushchim faktorom i gialuronidazoy [Mechanisms of mobilization of mesenchymal precursor cell under the effect of granulocytic colony-stimulating factor and hyaluronidase]. Byulleten’ eksperimental’noy biologii i meditsiny – Bulletin of Experimental Biology and Medicine. 2007; 144(12): 652-56 [in Russian].
70. Lian JB, Stein GS, Aubin JE. Bone formation: maturation and functional activities of osteoblast lineage cells. American Society for Bone and Mineral Research. 2003; 20(11): 13-28.
71. Ducy P, Schinke T, Karsenty G. The osteoblast: a sophisticated fibroblast under central surveillance. Science. 2000; 289(5484): 1501-04. https://doi.org/10.1126/science.289.5484.1501  PMid:10968779
72. Mackie EJ. Osteoblasts: novel roles in orchestration of skeletal architecture. Int J Biochem Cell Biol. 2003; 35(9): 1301-05. https://doi.org/10.1016/S1357-2725(03)00107-9
73. Dorheim MA, Sullivan M, Dandapani V, et al. Osteoblastic gene expression during adipose genesis in hematopoietic supporting murine bone marrow stromal cells. J Cell Phys. 1993; 154(2): 317-28.https://doi.org/10.1002/jcp.1041540215   PMid:8425912
74. Taichman RS, Emerson SG. Human osteoblasts support hematopoiesis through the production of granulocyte colony-stimulating factor. J Exp Med. 1994; 179(5): 1677-82.https://doi.org/10.1084/jem.179.5.1677
75. Taichman R, Reilly MJ, Emerson SG. Human osteoblasts support human hematopoietic progenitor cells in vitro bone marrow cultures. Blood. 1996; 87(2): 518-24.
76. Tachman RS, Emerson SG. The role of osteoblasts in the hematopoietic microenvironment. Stem Cells. 1998; 16(1): 7-15. https://doi.org/10.1002/stem.160007   PMid:9474743
77. Taichman RS, Reilly MJ, Emerson SG. The Hematopoietic Microenvironment: Osteoblasts and The Hematopoietic Microenvironment. Hematology. 2000; 4(5): 421-26.https://doi.org/10.1080/10245332.1999.11746468
78. Calvi LM, Adams GB, Weibrecht KW, et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003; 425(6960): 841–46. https://doi.org/10.1038/nature02040   PMid:14574413
79. Arai F, Hirao A, Ohmura M, et al. Tie2 Angiopoietin-1 Signaling Regulates Hematopoietic Stem Cell Quiescence in the Bone Marrow Niche. Cell. 2004; 118(2): 149-61.https://doi.org/10.1016/j.cell.2004.07.004   PMid:15260986
80. Visnjic D, Kalajzic Z, Rowe DW, et al. Hematopoiesis is severely altered in mice with an induced osteoblast deficiency. Blood. 2004; 103(9): 3258-64. https://doi.org/10.1182/blood-2003-11-4011  PMid:14726388
81. Bowers M, Zhang B, Ho Y, et al. Osteoblast ablation reduces normal long-term hematopoietic stem cell self-renewal but accelerates leukemia development. Blood. 2015; 125(17): 2678-88.https://doi.org/10.1182/blood-2014-06-582924   PMid:25742698      PMCid:PMC4408292
82. Osawa M, Hanada K, Hamada H, et al. Long-term lymphohematopoietic reconstitution by a single CD34-low negative hematopoietic stem cell. Science. 1996; 273(5272):242-45.https://doi.org/10.1126/science.273.5272.242   PMid:8662508
83. Nilsson SK, Johnston HM, Coverdale JA. Spatial localization of transplanted hematopoietic stem cells: inferences for the localization of stem cell niches. Blood. 2001; 97(8): 2293-99.https://doi.org/10.1182/blood.V97.8.2293   PMid:11290590
84. Wilson A, Murphy MJ, Oskarsson T, et al. c-Myc controls the balance between hematopoietic stem cell self-renewal and differentiation. Genes Dev. 2004; 18(22): 2747-63.https://doi.org/10.1101/gad.313104   PMid:15545632      PMCid:PMC528895
85. Xie Y, Yin T, Wiegraebe W, et al. Detection of functional haematopoietic stem cell niche using real time imaging. Nature. 2009; 457(7225): 97-101. https://doi.org/10.1038/nature07639  PMid:19052548
86. Zhu J, Garrett R, Jung Y, et al. Osteoblasts support B-lymphocyte commitment and differentiation from hematopoietic stem cells. Blood. 2007; 109(9): 3706-12. https://doi.org/10.1182/blood-2006-08-041384   PMid:17227831
87. Omatsu Y, Sugiyama T, Kohara H, et al. The essential functions of adipoosteogenic progenitors as the hematopoietic stem and progenitor cell niche. Immunity. 2010; 33(3): 387-99.https://doi.org/10.1016/j.immuni.2010.08.017   PMid:20850355
88. Li JY, Adams J, Calvi LM, et al. PTH expands short-term murine hematopoietic stem cells through T cells. Blood. 2012; 120(22): 4352-62. https://doi.org/10.1182/blood-2012-06-438531  PMid:22955916      PMCid:PMC3507144
89. Lymperi S, Horwood N, Marley S, et al. Strontium can increase some osteoblasts without increasing hematopoietic stem cells Blood. 2008; 111(3): 1173-81.
90. Ma YD, Park C, Zhao H, et al. Defects in osteoblast function but no changes in long-term repopulating potential of hematopoietic stem cells in a mouse chronic inflammatory arthritis model. Blood. 2009; 114(20): 4402-10. https://doi.org/10.1182/blood-2008-12-196311   PMid:19759358      PMCid:PMC2777125
91. Kiel MJ, Radice GL, Morrison SJ. Lack of Evidence that Hematopoietic Stem Cells Depend on N-Cadherin-Mediated Adhesion to Osteoblasts for Their Maintenance. Cell Stem Cell. 2007; 1(2): 204-17. https://doi.org/10.1016/j.stem.2007.06.001   PMid:18371351
92. Ding L, Morrison SJ. Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches. Nature. 2013; 495(7440): 231-5. https://doi.org/10.1038/nature11885  PMid:23434755      PMCid:PMC3600153
93. Greenbaum A, Hsu YM, Day RB, et al. CXCL12 in early mesenchymal progenitors is required for haematopoietic stem-cell maintenance. Nature. 2013; 495(7440): 227-30.https://doi.org/10.1038/nature11926   PMid:23434756      PMCid:PMC3600148
94. Ding L, Saunders TL, Enikolopov G, et al. Endothelial and perivascular cells maintain haematopoietic stem cells. Nature. 2012; 481(7382): 457-62. https://doi.org/10.1038/nature10783  PMid:22281595      PMCid:PMC3270376
95. Doulatov S, Notta F, Laurenti E, et al. Hematopoiesis: a human perspective. Cell Stem Cell. 2012; 10(2): 120-36. https://doi.org/10.1016/j.stem.2012.01.006   PMid:22305562
96. Nolan DJ, Ginsberg M, Israely E, et al. Molecular signatures of tissue-specific microvascular endothelial cell heterogeneity in organ maintenance and regeneration. Dev Cell. 2013; 26(2): 204-19.https://doi.org/10.1016/j.devcel.2013.06.017   PMid:23871589      PMCid:PMC3873200
97. Nakamura Y, Arai F, Iwasaki H, et al. Isolation and characterization of endosteal niche cell populations that regulate hematopoietic stem cells. Blood. 2010; 116(9): 1422-32.https://doi.org/10.1182/blood-2009-08-239194   PMid:20472830
98. Nagasawa T, Kikutani H, Kishimoto T. Molecular cloning and structure of a pre-B-cell growth-stimulating factor. Proc Natl Acad Sci USA.1994; 91(6): 2305-09. https://doi.org/10.1073/pnas.91.6.2305  PMid:8134392      PMCid:PMC43359
99. Nagasawa T, Hirota S, Tachibana K, et al. Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF SDF-1. Nature. 1996; 382(6592): 635-38.https://doi.org/10.1038/382635a0   PMid:8757135
100. Tachibana K, Hirota S, Iizasa H, et al. The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract. Nature. 1998; 393(6685): 591-94. https://doi.org/10.1038/31261  PMid:9634237
101. Zou YR, Kottmann AH, Kuroda M, et al. Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature. 1998; 393(6685): 595-99.https://doi.org/10.1038/31269   PMid:9634238
102. Ara T, Itoi M, Kawabata K, et al. A role of CXC chemokine ligand 12 stromal cell-derived factor-1 pre-B cell growth stimulating factor and its receptor CXCR4 in fetal and adult T cell development in vivo. J Immunol. 2003; 170(9): 4649-55. https://doi.org/10.4049/jimmunol.170.9.4649   PMid:12707343
103. Tokoyoda K, Egawa T, Sugiyama T, et al. Cellular niches controlling B lymphocyte behavior within bone marrow during development. Immunity. 2004; 20(6):707-18.https://doi.org/10.1016/j.immuni.2004.05.001   PMid:15189736
104. Nagasawa T. Microenvironmental niches in the bone marrow required for B-cell development. Nat Rev Immunol. 2006; 6(2): 107-16. https://doi.org/10.1038/nri1780   PMid:16491135
105. Sugiyama T, Kohara H, Noda M, et al. Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity. 2006; 25(6): 977-88.https://doi.org/10.1016/j.immuni.2006.10.016   PMid:17174120
106. Kohara H, Omatsu Y, Sugiyama T, et al. Development of plasmacytoid dendritic cells in bone marrow stromal cell niches requires CXCL12-CXCR4 chemokine signaling. Blood. 2007; 110(13): 4153-60. https://doi.org/10.1182/blood-2007-04-084210   PMid:17827391
107. Noda M, Omatsu Y, Sugiyama T, et al. CXCL12-CXCR4 chemokine signaling is essential for NK-cell development in adult mice. Blood. 2010; 117(2): 451-58. https://doi.org/10.1182/blood-2010-04-277897   PMid:20944068
108. Maes C, Kobayashi T, Selig MK, et al. Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels. Dev Cell. 2010; 19(2): 329-44.https://doi.org/10.1016/j.devcel.2010.07.010   PMid:20708594      PMCid:PMC3540406
109. Liu Y, Strecker S, Wang L, et al. Osterix-cre labeled progenitor cells contribute to the formation and maintenance of the bone marrow stroma. PLoS ONE. 2013; 8(8): e71318.
110. Nakashima K, Zhou X, Kunkel G, et al. The novel zinc finger–containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell. 2002; 108(1): 17-29.https://doi.org/10.1016/S0092-8674(01)00622-5
111. Jung Y, Wang J, Schneider A, et al. Regulation of SDF-1 (CXCL12) production by osteoblasts; a possible mechanism for stem cell homing. Bone. 2006; 38(4): 497-508.https://doi.org/10.1016/j.bone.2005.10.003   PMid:16337237
112. Kiel MJ, Acar M, Radice GL, et al. Hematopoietic stem cells do not depend on N-cadherin to regulate their maintenance. Cell Stem Cell. 2009; 4(2): 170-79.https://doi.org/10.1016/j.stem.2008.10.005   PMid:19119091      PMCid:PMC2681089
113. Greenbaum AM, Revollo LD, Woloszynek JR, et al. N-cadherin in osteolineage cells is not required for maintenance of hematopoietic stem cells. Blood. 2012; 120(2): 295-302.https://doi.org/10.1182/blood-2011-09-377457   PMid:22323481      PMCid:PMC3398761
114. Bromberg O, Frisch BJ, Weber JM, et al. Osteoblastic N-cadherin is not required for microenvironmental support and regulation of hematopoietic stem and progenitor cells. Blood. 2012; 120(2): 303-13. https://doi.org/10.1182/blood-2011-09-377853   PMid:22596259      PMCid:PMC3398755
115. Hosokawa K, Arai F, Yoshihara H, et al. Cadherin-based adhesion is a potential target for niche manipulation to protect hematopoietic stem cells in adult bone marrow. Cell Stem Cell. 2010; 6(3): 194-98. https://doi.org/10.1016/j.stem.2009.04.013   PMid:20207221
116. Hosokawa K, Arai F, Yoshihara H, et al. Knockdown of N-cadherin suppresses the long-term engraftment of hematopoietic stem cells. Blood. 2010; 116(4): 554-63. https://doi.org/10.1182/blood-2009-05-224857   PMid:20427705
117. Stier S, Ko Y, Forkert R, et al. Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size. J Exp Med. 2005; 201(11): 1781-91.https://doi.org/10.1084/jem.20041992   PMid:15928197      PMCid:PMC2213260
118. Qian H, Buza-Vidas N, Hyland CD, et al. Critical role of thrombopoietin in maintaining adult quiescent hematopoietic stem cells. Cell Stem Cell. 2007; 1(6): 671-84.https://doi.org/10.1016/j.stem.2007.10.008   PMid:18371408
119. Yoshihara H, Arai F, Hosokawa K, et al. Thrombopoietin MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche. Cell Stem Cell. 2007; 1(6): 685-97.https://doi.org/10.1016/j.stem.2007.10.020   PMid:18371409
120. Zhou BO, Ding L, Morrison SJ. Hematopoietic stem and progenitor cells regulate the regeneration of their niche by secreting Angiopoietin-1. Elife. 2015; 4. Available: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4411515/.
121. Adams GB, Chabner KT, Alley IR, et al. Stem cell engraftment at the endosteal niche is specified by the calcium-sensing receptor. Nature. 2006; 439(7076): 599-603.https://doi.org/10.1038/nature04247   PMid:16382241
122. Mancini SJ, Mantei N, Dumortier A, et al. Jagged1-dependent Notch signaling is dispensable for hematopoietic stem cell self-renewal and differentiation. Blood. 2005; 105(6): 2340-42.https://doi.org/10.1182/blood-2004-08-3207   PMid:15550486
123. Nilsson SK, Johnston HM, Whitty GA, et al. Osteopontin, a key component of the hematopoietic stem cell niche and regulator of primitive hematopoietic progenitor cells. Blood. 2005; 106(4): 1232-39. https://doi.org/10.1182/blood-2004-11-4422   PMid:15845900
124. Adams GB, Scadden DT. The hematopoietic stem cells in its place. Nat Immunol. 2006; 7: 333-37. https://doi.org/10.1038/ni1331   PMid:16550195
125. Yin T, Li L. The stem cell niches in bone. Journal of Clinical Investigation. 2006; 116(5): 1195-201. https://doi.org/10.1172/JCI28568   PMid:16670760      PMCid:PMC1451221
126. Fleming HE, Janzen V, Lo Celso C, et al. Wnt signaling in the niche enforces hematopoietic stem cell quiescence and is necessary to preserve self-renewal in vivo. Cell Stem Cell. 2008; 2(2): 274-83.https://doi.org/10.1016/j.stem.2008.01.003   PMid:18371452      PMCid:PMC2991120
127. Kiel MJ, Morrison SJ. Uncertainty in the niches that maintain haematopoietic stem cells. Nat Rev Immunol. 2008; 8(4): 290-301. https://doi.org/10.1038/nri2279   PMid:18323850
128. Ceradini DJ, Kulkarni AR, Callaghan MJ, et al. Progenitor cell trafficking is regulated by hypoxic gradients throughHIF-1 induction of SDF-1. Nat Med. 2004; 10(8): 858-64.https://doi.org/10.1038/nm1075   PMid:15235597
129. Broxmeyer HE, Orschell CM, Clapp DW, et al. Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist. J Exp Med. 2005; 201(8): 1307-18. https://doi.org/10.1084/jem.20041385   PMid:15837815      PMCid:PMC2213145
130. Karpova D, Bonig H. Concise Review: CXCR4 CXCL12 Signaling in Immature Hematopoiesis – Lessons From Pharmacological and Genetic Models. Stem Cells. 2015; 33(8):2391-99.https://doi.org/10.1002/stem.2054   PMid:25966814
131. Lapidot T, Dar A, Kollet O. How do stem cells find their way home? Blood. 2005; 106(6): 1901-1910. https://doi.org/10.1182/blood-2005-04-1417   PMid:15890683
132. Askenasy N, Farkas DL. In vivo imaging studies of the effect of recipient conditioning, donor cell phenotype and antigen disparity on homing of haematopoietic cells to the bone marrow. British Journal of Haematology. 2003; 120(3): 505-15. https://doi.org/10.1046/j.1365-2141.2003.04114.x   PMid:12580970
133. Wang JC, Doedens M, Dick JE. Primitive human hematopoietic cells are enriched in cord blood compared with adult bone marrow or mobilized peripheral blood as measured by the quantitative in vivo SCID-repopulating cell assay. Blood. 1997; 89(11)3919-24.
134. De Barros AP, Takiya CM, Garzoni LR, et al. Osteoblasts and bone marrow mesenchymal stromal cells control hematopoietic stem cell migration and proliferation in 3D in vitro model. PLoS One. 2010; 5. Available: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816998/.
135. Kiel MJ, He S, Ashkenazi R, et al. Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU. Nature. 2007; 449(7159): 238-42. https://doi.org/10.1038/nature06115  PMid:17728714      PMCid:PMC2633872
136. McCabe A, Zhang Y, Thai V, et al. Macrophage-Lineage Cells Negatively Regulate the Hematopoietic Stem Cell Pool in Response to Interferon Gamma at Steady State and During Infection.Stem Cells. 2015; 33(7): 2294-2305. https://doi.org/10.1002/stem.2040   PMid:25880153      PMCid:PMC4693298
137. Goodell MA, Brose K, Paradis G, et al. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med. 1996; 183(4): 1797-1806.https://doi.org/10.1084/jem.183.4.1797   PMid:8666936
138. Zhou S, Schuetz JD, Bunting KD, et al. The ABC transporter Bcrp1 ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med. 2001; 7(9): 1028-34. https://doi.org/10.1038/nm0901-1028   PMid:11533706
139. Huttmann A, Liu SL, Boyd AW, et al. Functional heterogeneity within rhodamine123(lo) Hoechst33342(losp) primitive hematopoietic stem cells revealed by pyroninY. Exp Hematol. 2001; 29(9): 09-1116. https://doi.org/10.1016/S0301-472X(01)00684-1
140. Wilson A, Oser GM, Jaworski M, et al. Dormant and self-renewing hematopoietic stem cells and their niches. Ann NY Acad Sci. 2007; 1106(1): 64-75. https://doi.org/10.1196/annals.1392.021  PMid:17442778
141. Haug JS, He XC, Grindley JC, et al. N-cadherin expression level distinguishes reserved versus primed states of hematopoietic stem cells. Cell Stem Cell. 2008; 2(4): 367-79.https://doi.org/10.1016/j.stem.2008.01.017   PMid:18397756
142. Cao J, Zhang L, Wan Y, et al. Ablation of Wnt less in endosteal niches impairs lymphopoiesis rather than HSCs maintenance. Eur J Immunol. 2015; 45(9): 2650-60.https://doi.org/10.1002/eji.201445405   PMid:26173091
143. Kunisaki Y, Bruns I, Scheiermann C, et al. Arteriolar niches maintain haematopoietic stem cell quiescence. Nature. 2013; 502(7473): 637-43. https://doi.org/10.1038/nature12612   PMid:24107994      PMCid:PMC3821873
144. Hackney JA, Charbord P, Brunk BP, et al. A molecular profile of a hematopoietic stem cell niche. Proc Natl Acad Sci USA. 2002; 99(20): 13061-66. https://doi.org/10.1073/pnas.192124499  PMid:12226475      PMCid:PMC130586
145. Mendelson A, Frenette PS. Hematopoietic stem cell niche maintenance during homeostasis and regeneration. Nat Med. 2014; 20(8): 833-46. https://doi.org/10.1038/nm.3647   PMid:25100529      PMCid:PMC4459580
146. Mehta A, Zhao JL, Sinha N, et al. The MicroRNA-132 and MicroRNA-212 Cluster Regulates Hematopoietic Stem Cell Maintenance and Survival with Age by Buffering FOXO3 Expression. Immunity. 2015; 42(6): 1021-32. https://doi.org/10.1016/j.immuni.2015.05.017   PMid:26084022      PMCid:PMC4471877
147. Lo Celso C, Fleming HE, Wu JW, et al. Live animal tracking of individual haematopoietic stem progenitor cells in their niche. Nature. 2009; 457(7225): 92-6. https://doi.org/10.1038/nature07434  PMid:19052546      PMCid:PMC2820276
148. Hooper AT, Butler JM, Nolan DJ, et al. Engraftment and reconstitution of hematopoiesis is dependent on VEGFR2-mediated regeneration of sinusoidal endothelial cells. Cell Stem Cell. 2009; 4(3): 263-74. https://doi.org/10.1016/j.stem.2009.01.006   PMid:19265665      PMCid:PMC3228275
149. Katayama Y, Battista M, Kao WM, et al. Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow. Cell. 2006; 124(2): 407-21.https://doi.org/10.1016/j.cell.2005.10.041   PMid:16439213
150. Mendez- S Ferrer, Lucas D, Battista M, et al. Haematopoietic stem cell release is regulated by circadian oscillations. Nature. 2008; 452(7186): 442-47. https://doi.org/10.1038/nature06685  PMid:18256599
151. Lucas D, Scheiermann C, Chow A, et al. Chemotherapy-induced bone marrow nerve injury impairs hematopoietic regeneration. Nat Med. 2013; 19(6): 695-703. https://doi.org/10.1038/nm.3155  PMid:23644514      PMCid:PMC3964478
152. Mendez-Ferrer S, Battista M, Frenette PS. Cooperation of beta(2)- and beta(3)-adrenergic receptors in hematopoietic progenitor cell mobilization. Ann NY Acad Sci. 2010; 1192(1): 139-44.https://doi.org/10.1111/j.1749-6632.2010.05390.x   PMid:20392229      PMCid:PMC4106131
153. Mendez-Ferrer S, Michurina TV, Ferraro F, et al. Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature. 2010; 466(7308): 829-34. https://doi.org/10.1038/nature09262  PMid:20703299      PMCid:PMC3146551
154. Park D, Spencer JA, Koh BI, et al. Endogenous bone marrow MSCs are dynamic, fate-restricted participants in bone maintenance and regeneration. Cell Stem Cell. 2012; 10(3): 259-72.https://doi.org/10.1016/j.stem.2012.02.003   PMid:22385654      PMCid:PMC3652251
155. Joseph C, Quach JM, Walkley CR, et al. Deciphering hematopoietic stem cells in their niches: a critical appraisal of genetic models, lineage tracing, and imaging strategies. Cell Stem Cell. 2013; 13(5): 520-33. https://doi.org/10.1016/j.stem.2013.10.010   PMid:24209759
156. Pinho S, Lacombe J, Hanoun M, et al. PDGFR? and CD51 mark human nestin+ sphere-forming mesenchymal stem cells capable of hematopoietic progenitor cell expansion. J Exp Med. 2013; 210(7): 1351-67. https://doi.org/10.1084/jem.20122252   PMid:23776077      PMCid:PMC3698522
157. Mizoguchi T, Pinho S, Ahmed J, et al. Osterix marks distinct waves of primitive and definitive stromal progenitors during bone marrow development. Dev Cell. 2014; 29(3): 340-49.https://doi.org/10.1016/j.devcel.2014.03.013   PMid:24823377      PMCid:PMC4051418
158. Zhou BO, Yue R, Murphy MM, et al. Leptin-receptor-expressing mesenchymal stromal cells represent the main source of bone formed by adult bone marrow. Cell Stem Cell. 2014; 15(2): 154-68.https://doi.org/10.1016/j.stem.2014.06.008   PMid:24953181      PMCid:PMC4127103
159. Saito M, Iwawaki T, Taya C, et al. Diphtheria toxin receptor-mediated conditional and targeted cell ablation in transgenic mice. Nat Biotechnol. 2001; 19(8): 746-50. https://doi.org/10.1038/90795  PMid:11479567
160. Sacchetti B, Funari A, Michienzi S, et al. Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell. 2007; 131(2): 324-36.https://doi.org/10.1016/j.cell.2007.08.025   PMid:17956733
161. Lendahl U, Zimmerman LB, McKay RD. CNS stem cells express a new class of intermediate filament protein. Cell. 1990; 60(4): 585-95. https://doi.org/10.1016/0092-8674(90)90662-X
162. Day K, Shefer G, Richardson JB, et al. Nestin-GFP reporter expression defines the quiescent state of skeletal muscle satellite cells. Dev Biol. 2007; 304(1): 246-59.https://doi.org/10.1016/j.ydbio.2006.12.026   PMid:17239845      PMCid:PMC1888564
163. Kfoury Y, Scadden DT. Mesenchymal cell contributions to the stem cell niche. Cell Stem Cell. 2015; 16(3): 239-53. https://doi.org/10.1016/j.stem.2015.02.019   PMid:25748931
164. Lenertz LY, Baughman CJ, Waldschmidt NV, et al. Control of bone development by P2X and P2Y receptors expressed in mesenchymal and hematopoietic cells. Gene. 2015; 570(1): 1-7.https://doi.org/10.1016/j.gene.2015.06.031   PMid:26079571
165. Ziegler P, Boettcher S, Takizawa H, et al. LPS-stimulated human bone marrow stroma cells support myeloid cell development and progenitor cell maintenance. Ann Hematol. 2016; 95(2): 173-78.https://doi.org/10.1007/s00277-015-2550-5   PMid:26555286
166. Chan CK, Chen CC, Luppen C. A, et al. Endochondral ossification is required for haematopoietic stem-cell niche formation. Nature. 2009; 457(7228): 490-94. https://doi.org/10.1038/nature07547  PMid:19078959      PMCid:PMC2648141
167. Morikawa S, Mabuchi Y, Kubota Y, et al. Prospective identification, isolation, and systemic transplantation of multipotent mesenchymal stem cells in murine bone marrow. J Exp Med. 2009; 206(11): 2483-96. https://doi.org/10.1084/jem.20091046   PMid:19841085      PMCid:PMC2768869
168. Wagner W, Roderburg C, Wein F, et al. Molecular and secretory profiles of human mesenchymal stromal cells and their abilities to maintain primitive hematopoietic progenitors. Stem Cells. 2007; 25(10): 2638-47. https://doi.org/10.1634/stemcells.2007-0280   PMid:17615262
169. De Bruyn PP, Breen PC, Thomas TB. The microcirculation of the bone marrow. Anat Rec. 1970; 168(1): 55-68. https://doi.org/10.1002/ar.1091680105   PMid:4918907
170. Acar M, Kocherlakota KS, Murphy MM, et al. Deep imaging of bone marrow shows non-dividing stem cells are mainly perisinusoidal. Nature. 2015; 526(7571): 126-30.https://doi.org/10.1038/nature15250   PMid:26416744      PMCid:PMC4850557
171. Chen JY, Miyanishi M, Wang SK, et al. Hoxb5 marks long-term haematopoietic stem cells and reveals a homogenous perivascular niche. Nature. 2016; 530: 223-27https://doi.org/10.1038/nature16943   PMid:26863982      PMCid:PMC4854608
172. Kennedy M, Firpo M, Choi K, et al. A common precursor for primitive erythropoiesis and definitive haematopoiesis. Nature. 1997; 386(6624): 488-93. https://doi.org/10.1038/386488a0  PMid:9087406
173. Shalaby F, Rossant J, Yamaguchi TP, et al. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature. 1995; 376(6535): 62-6. https://doi.org/10.1038/376062a0  PMid:7596435
174. Kobayashi H, Butler JM, O’Donnell R, et al. Angiocrine factors from Akt-activated endothelial cells balance self-renewal and differentiation of haematopoietic stem cells. Nat Cell Biol. 2010; 12(11): 1046-56 https://doi.org/10.1038/ncb2108   PMid:20972423      PMCid:PMC2972406
175. Himburg HA, Harris JR, Ito T, et al. Pleiotrophin regulates the retention and self-renewal of hematopoietic stem cells in the bone marrow vascular niche. Cell Reports. 2012; 2(4): 964-75.https://doi.org/10.1016/j.celrep.2012.09.002   PMid:23084748      PMCid:PMC3696585
176. Doan PL, Himburg HA, Helms K, et al. Epidermal growth factor regulates hematopoietic regeneration after radiation injury. Nat Med. 2013; 19(3): 295-304. https://doi.org/10.1038/nm.3070  PMid:23377280      PMCid:PMC3594347
177. Butler JM, Nolan DJ, Vertes EL, et al. Endothelial cells are essential for the self-renewal and repopulation of Notch-dependent hematopoietic stem cells. Cell Stem Cell. 2010; 6(3): 251-64.https://doi.org/10.1016/j.stem.2010.02.001   PMid:20207228      PMCid:PMC2866527
178. Poulos MG, Guo P, Kofler NM, et al. Endothelial Jagged-1 is necessary for homeostatic and regenerative hematopoiesis. Cell Reports. 2013; 4(5): 1022–34.https://doi.org/10.1016/j.celrep.2013.07.048   PMid:24012753      PMCid:PMC3805263
179. Kusumbe AP, Ramasamy SK, Adams RH. Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone. Nature. 2014; 507(7492): 323-28. https://doi.org/10.1038/nature13145  PMid:24646994      PMCid:PMC4943525
180. Ramasamy SK, Kusumbe AP, Wang L, et al. Endothelial Notch activity promotes angiogenesis and osteogenesis in bone. Nature. 2014; 507(7492): 376-80. https://doi.org/10.1038/nature13146  PMid:24647000      PMCid:PMC4943529
181. Rafii S. Shapiro F, Pettengell R, et al. Human bone marrow microvascular endothelial cells support long-term proliferation and differentiation of myeloid and megakaryocytic progenitors. Blood. 1995; 86(9): 3353-63.
182. 182. Chute JP, Saini AA, Chute DJ, et al. Ex vivo culture with human brain endothelial cells increases the SCID-repopulating capacity of adult human bone marrow. Blood. 2002; 100(13): 4433-39.https://doi.org/10.1182/blood-2002-04-1238   PMid:12393435
183. Li B, Bailey AS, Jiang S, et al. Endothelial cells mediate the regeneration of hematopoietic stem cells. Stem Cell Res. 2010; 4(1): 17-24. https://doi.org/10.1016/j.scr.2009.08.001   PMid:19720572      PMCid:PMC2938793
184. Winkler IG, Pettit AR, Raggatt LJ, et al. Hematopoietic stem cell mobilizing agents G-CSF, cyclophosphamide or AMD3100 have distinct mechanisms of action on bone marrow HSCs niches and bone formation. Leukemia. 2012; 26(7): 1594-601. https://doi.org/10.1038/leu.2012.17   PMid:22266913
185. Suda T, Takubo K, Semenza GL. Metabolic regulation of hematopoietic stem cells in the hypoxic niche. Cell Stem Cell. 2011; 9(4): 298-310. https://doi.org/10.1016/j.stem.2011.09.010  PMid:21982230
186. Nikolsky I, Serebrovska TV. Role of hypoxia in stem cell development and functioning Фізіологічний журнал. 2009; 55(4): 116-30.
187. Serebrovska T, Nikolsky I, Ishchuk V. Human Adaptation to Intermittent Hypoxia: Effects on Hematopoietic Stem Cells and Immune Function. Adaptation Biology and Medicine. 2011; 6: 181-91.
188. Nombela-Arrieta C, Silberstein LE. The science behind the hypoxic niche of hematopoietic stem and progenitors. Hematology Am Soc Hematol Educ Program. 2014; 2014(1): 542-47.https://doi.org/10.1182/asheducation-2014.1.542
189. Cipolleschi MG, Dello Sbarba PP, Olivotto M. The role of hypoxia in the maintenance of hematopoietic stem cells. Blood. 1993; 82(7): 2031-37.
190. Ivanovic Z, Dello Sbarba P, Trimoreau F, et al. Primitive human HPCs are better maintained and expanded in vitro at 1 percent oxygen than at 20 percent. Transfusion. 2000; 40(12): 1482-88.https://doi.org/10.1046/j.1537-2995.2000.40121482.x   PMid:11134568
191. Danet GH, Pan Y, Luongo JL, et al. Expansion of human SCID-repopulating cells under hypoxic conditions. J Clin Invest. 2003; 112(1): 126-35. https://doi.org/10.1172/JCI17669   PMid:12840067      PMCid:PMC162287
192. Chow DC, Wenning LA, Miller WM, et al. Modeling pO(2) distributions in the bone marrow hematopoietic compartment. II. Modified Kroghian models. Biophys J. 2001; 81(2): 685-96.https://doi.org/10.1016/S0006-3495(01)75733-5
193. Durand RE, Chaplin DJ, Olive PL. Cell sorting with Hoechst or carbocyanine dyes as perfusion probes in spheroids and tumors. Methods Cell Biol. 1990; 33: 509-18. https://doi.org/10.1016/S0091-679X(08)60550-6
194. Bernsen HJ, Rijken PF, Peters H, et al. Hypoxia in a human intracerebral glioma model. J Neurosurg. 2000; 93(3): 449-54. https://doi.org/10.3171/jns.2000.93.3.0449   PMid:10969943
195. Van Laarhoven HW, Bussink J, Lok J, et al. Effects of nicotinamide and carbogen in different murine colon carcinomas: immunohistochemical analysis of vascular architecture and microenvironmental parameters. Int J Radiat Oncol Biol Phys. 2004; 60(1): 310-21. https://doi.org/10.1016/j.ijrobp.2004.05.014   PMid:15337570
196. Olive PL, Durand RE, Raleigh JA, et al. Comparison between the comet assay and pimonidazole binding for measuring tumour hypoxia. Br J Cancer. 2000; 83(11): 1525-31.https://doi.org/10.1054/bjoc.2000.1489   PMid:11076663      PMCid:PMC2363410
197. Olive PL, Luo CM, Banath JP. Local hypoxia is produced at sites of intratumour injection. Br J Cancer. 2002; 86(3): 429-35. https://doi.org/10.1038/sj.bjc.6600059   PMid:11875711      PMCid:PMC2375199
198. Parmar K, Mauch P, Vergilio JA, et al. Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxia. Proc Natl Acad Sci USA. 2007; 104(13): 5431-36.https://doi.org/10.1073/pnas.0701152104   PMid:17374716      PMCid:PMC1838452
199. Hale LP, Braun RD, Gwinn WM, et al. Hypoxia in the thymus: role of oxygen tension in thymocyte survival. Am J Physiol Heart Circ Physiol. 2002; 282(4): H1467-77.
200. Winkler IG, Barbier V, Wadley R, et al. Positioning of bone marrow hematopoietic and stromal cells relative to blood flow in vivo: serially reconstituting hematopoietic stem cells reside in distinct non perfused niches. Blood. 2010; 116(3): 375-85. https://doi.org/10.1182/blood-2009-07-233437   PMid:20393133
201. Parmar K, Sauk-Schubert C, Burdick D, et al. Sca+CD34- murine side population cells are highly enriched for primitive stem cells Exp Hematol. 2003; 31(3): 244-50.
202. Raleigh JA, Dewhirst MW, Thrall DE. Measuring Tumor Hypoxia. Semin Radiat Oncol. 1996; 6(1): 37-45. https://doi.org/10.1016/S1053-4296(96)80034-8
203. Goodell MA, Rosenzweig M, Kim H, et al. Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species. Nat Med. 1997; 3(12): 1337-45. https://doi.org/10.1038/nm1297-1337   PMid:9396603
204. Matsuzaki Y, Kinjo K, Mulligan RC, et al. Unexpectedly efficient homing capacity of purified murine hematopoietic stem cells. Immunity. 2004; 20(1): 87-93. https://doi.org/10.1016/S1074-7613(03)00354-6
205. Brown JM, Wilson WR. Exploiting tumor hypoxia in cancer treatment. Nat Rev Cancer. 2004; 4(6): 437-47. https://doi.org/10.1038/nrc1367   PMid:15170446
206. Jang YY, Sharkis SJ. A low level of reactive oxygen species selects for primitive hematopoietic stem cells that may reside in the low-oxygenic niche. Blood. 2007; 110(8): 3056-63.https://doi.org/10.1182/blood-2007-05-087759   PMid:17595331      PMCid:PMC2018677
207. Unwin RD, Smith DL, Blinco D, et al. Quantitative proteomics reveals posttranslational control as a regulatory factor in primary hematopoietic stem cells. Blood. 2006; 107(12): 4687-94.https://doi.org/10.1182/blood-2005-12-4995   PMid:16507774
208. Pearce DJ, Ridler CM, Simpson C, et al. Multiparameter analysis of murine bone marrow side population cells. Blood. 2004; 103(7): 2541-46. https://doi.org/10.1182/blood-2003-09-3281  PMid:14644998
209. Camargo FD, Chambers SM, Drew E, et al. Hematopoietic stem cells do not engraft with absolute efficiencies. Blood. 2006; 107(2): 501-7. https://doi.org/10.1182/blood-2005-02-0655  PMid:16204316      PMCid:PMC1895609
210. Nishi H, Nakada T, Kyo S, et al. Hypoxia-inducible factor 1 mediates upregulation of telomerase (hTERT). Mol Cell Biol. 2004; 24(13): 6076-83. https://doi.org/10.1128/MCB.24.13.6076-6083.2004  PMid:15199161      PMCid:PMC480902
211. Yatabe N, Kyo S, Maida Y, et al. HIF-1-mediated activation of telomerase in cervical cancer cells. Oncogene. 2004; 23(20): 3708-15. https://doi.org/10.1038/sj.onc.1207460   PMid:15048086
212. Covello KL, Kehler J, Yu H, et al. HIF-2alpha regulates Oct-4: effects of hypoxia on stem cell function, embryonic development, and tumor growth. Genes Dev. 2006; 20(5): 557-70.https://doi.org/10.1101/gad.1399906   PMid:16510872      PMCid:PMC1410808
213. Takubo K, Goda N, Yamada W, et al. Regulation of the HIF-1alpha level is essential for hematopoietic stem cells Cell Stem Cell. 2010; 7(3): 391-402.
214. Forristal CE, Winkler IG, Nowlan B, et al. Pharmacologic stabilization of HIF-1alpha increases hematopoietic stem cell quiescence in vivo and accelerates blood recovery after severe irradiation. Blood. 2013; 121(5): 759-69. https://doi.org/10.1182/blood-2012-02-408419   PMid:23243286
215. Schajnovitz A, Itkin T, D’Uva G, et al. CXCL12 secretion by bone marrow stromal cells is dependent on cell contact and mediated by connexin-43 and connexin-45 gap junctions. Nat Immunol. 2011; 12(5): 391-98. https://doi.org/10.1038/ni.2017   PMid:21441933
216. Heinrich MC, Dooley DC, Freed AC, et al. Constitutive expression of steel factor gene by human stromal cells. Blood. 1993; 82(3): 771-83.
217. Blair HC, Julian BA, Cao X, et al. Parathyroid hormone-regulated production of stem cell factor in human osteoblasts and osteoblast-like cells. Biochem Biophys Res Commun. 1999; 255(3): 778-84.https://doi.org/10.1006/bbrc.1999.0260   PMid:10049787
218. Kimura Y, Ding B, Imai N, et al. c-Kit-Mediated Functional Positioning of Stem Cells to Their Niches Is Essential for Maintenance and Regeneration of Adult Hematopoiesis. PLoS One. 2011; DOI: 10.1371 journal.pone.0026918
219. Blank U, Karlsson S. TGF-? signaling in the control of hematopoietic stem cells. Blood. 2015; 125(23): 3542-50. https://doi.org/10.1182/blood-2014-12-618090   PMid:25833962
220. Yamazaki S, Ema H, Karlsson G, et al. Non myelinating Schwann cells maintain hematopoietic stem cell hibernation in the bone marrow niche. Cell. 2011; 147(5): 1146-58.https://doi.org/10.1016/j.cell.2011.09.053   PMid:22118468
221. Challen GA, Boles NC, Chambers SM, et al. Distinct hematopoietic stem cell subtypes are differentially regulated by TGF?1. Cell Stem Cell. 2010; 6(3): 265-78.https://doi.org/10.1016/j.stem.2010.02.002   PMid:20207229      PMCid:PMC2837284
222. Brenet F, Kermani P, Spektor R, et al. TGF? restores hematopoietic homeostasis after myelosuppressive chemotherapy. J Exp Med. 2013; 210(3): 623-39. https://doi.org/10.1084/jem.20121610  PMid:23440043      PMCid:PMC3600905
223. Miharada K, Karlsson G, Rehn M, et al. Cripto regulates hematopoietic stem cells as a hypoxic-niche- related factor through cell surface receptor GRP78. Cell Stem Cell. 2011; 9(4): 330-44.https://doi.org/10.1016/j.stem.2011.07.016   PMid:21982233
224. Bhardwaj G, Murdoch B, Wu D, et al. Sonic hedgehog induces the proliferation of primitive human hematopoietic cells via BMP regulation. Nat Immunol. 2001; 2(2): 172-80.https://doi.org/10.1038/84282   PMid:11175816
225. Pajcini KV, Speck NA, Pear WS. Notch signaling in mammalian hematopoietic stem cells. Leukemia. 2011; 25(10): 1525-32. https://doi.org/10.1038/leu.2011.127   PMid:21647159
226. Bigas A, Espinosa L. Hematopoietic stem cells: to be or Notch to be. Blood. 2012; 119(14): 3226-35. https://doi.org/10.1182/blood-2011-10-355826   PMid:22308291
227. Stier S, Cheng T, Dombkowski D, et al. Notch1 activation increases hematopoietic stem cell self-renewal in vivo and favors lymphoid over myeloid lineage outcome. Blood. 2002; 99(7): 2369-78.https://doi.org/10.1182/blood.V99.7.2369   PMid:11895769
228. Jacobsen S. Defining ‘stemness’: Notch and Wnt join forces? Nat. Immunol. 2005; 6(3): 234-36. https://doi.org/10.1038/ni0305-234
229. Lin MI, Price EN, Boatman S, et al. Angiopoietin-like proteins stimulate HSPC development through interaction with notch receptor signaling. Elife. 2015; 25. Available: http:.www.ncbi.nlm.nih.gov/pmc/articles/PMC4371382
230. Duncan AW, Rattis FM, DiMascio LN, et al. Integration of Notch and Wnt signaling in hematopoietic stem cell maintenance. Nat Immunol. 2005; 6(3): 314-22. https://doi.org/10.1038/ni1164  PMid:15665828
231. Maillard I, Koch U, Dumortier A, et al. Canonical Notch signaling is dispensable for the maintenance of adult hematopoietic stem cells. Cell Stem Cell. 2008; 2(4): 356-66.https://doi.org/10.1016/j.stem.2008.02.011   PMid:18397755      PMCid:PMC3717373
232. Varnum-Finney B, Halasz LM, Sun M, et al. Notch2 governs the rate of generation of mouse long- and short-term repopulating stem cells. J Clin Invest. 2011; 121(3): 1207-16.https://doi.org/10.1172/JCI43868   PMid:21285514      PMCid:PMC3049401
233. Oh P, Lobry C, Gao J, et al. In vivo mapping of notch pathway activity in normal and stress hematopoiesis Cell Stem Cell. 2013; 13(2): 190-204.
234. Mercher T, Cornejo MG, Sears C, et al. Notch signaling specifies megakaryocyte development from hematopoietic stem cells. Cell Stem Cell. 2008; 3(3): 314-26.https://doi.org/10.1016/j.stem.2008.07.010   PMid:18786418      PMCid:PMC3970322
235. 235. Malhotra S, Kincade PW. Wnt-related molecules and signaling pathway equilibrium in hematopoiesis. Cell Stem Cell. 2009; 4(1): 27-36. https://doi.org/10.1016/j.stem.2008.12.004  PMid:19128790      PMCid:PMC2975490
236. Kabiri Z. Numata A, Kawasaki A, et al. Wnts are dispensable for differentiation and self-renewal of adult murine hematopoietic stem cells. Blood. 2015; 126(9): 1086-94.https://doi.org/10.1182/blood-2014-09-598540   PMid:26089398      PMCid:PMC4598194
237. Reya T, Duncan AW, Ailles L, et al. A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature. 2003; 423(6938): 409-14. https://doi.org/10.1038/nature01593   PMid:12717450
238. Willert K, Brown JD, Danenberg E, et al. Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature. 2003; 423(6938): 448-52. https://doi.org/10.1038/nature01611  PMid:12717451
239. Luis TC, Weerkamp F, Naber BA, et al. Wnt3a deficiency irreversibly impairs hematopoietic stem cell self-renewal and leads to defects in progenitor cell differentiation. Blood. 2009; 113(3): 546-54.https://doi.org/10.1182/blood-2008-06-163774   PMid:18832654
240. Nemeth MJ, Topol L, Anderson SM, et al. Wnt5a inhibits canonical Wnt signaling in hematopoietic stem cells and enhances repopulation. Proc Natl Acad Sci USA. 2007; 104(39): 15436-441.https://doi.org/10.1073/pnas.0704747104   PMid:17881570      PMCid:PMC1986571
241. Povinelli BJ, Nemeth MJ. Wnt5a regulates hematopoietic stem cell proliferation and repopulation through the Ryk receptor. Stem Cells. 2014; 32(1): 105-15. https://doi.org/10.1002/stem.1513  PMid:23939973
242. Abidin BM, Owusu KE, Heinonen KM. Frizzled-6 Regulates Hematopoietic Stem Progenitor Cell Survival and Self-Renewal. J Immunol. 2015; 195(5): 2168-76.https://doi.org/10.4049/jimmunol.1403213   PMid:26188064
243. Sugimura R, He XC, Venkatraman A, et al. Non canonical Wnt signaling maintains hematopoietic stem cells in the niche. Cell. 2012; 150(2): 351-65. https://doi.org/10.1016/j.cell.2012.05.041  PMid:22817897      PMCid:PMC4492542
244. Luis TC, Naber BA, Roozen PP, et al. Canonical Wnt signaling regulates hematopoiesis in a dosage dependent fashion. Cell Stem Cell. 2011; 9(4): 345-56. https://doi.org/10.1016/j.stem.2011.07.017  PMid:21982234
245. Оrlovskaya IA, Toporkova LB. Geneticheskie programmy regulyatsii samopodderzhaniya gemopoeticheskikh stvolovykh kletok [Genetic programs of regulation of self-maintenance of hematopoietic stem cells]. Rossiyskiy immunologicheskiy zhurnal – Russian Journal of Immunology. 2008; 2(11)(2): 114 [in Russian].
246. Toporkova LB, Оrlovskaya IA, Khaldoyanidi SK. Mekhanizmy regulyatsii samopodderzhaniya gemopoeticheskoy stvolovoy kletki [Mechanisms of regulation of self- maintenance of hematopoietic stem cells]. Uspekhi sovremennoy biologii – Biology Bulletin Reviews. 2008; 128(5): 458-66 [in Russian].
247. Bruns I, Lucas D, Pinho S, et al. Megakaryocytes regulate hematopoietic stem cell quiescence through CXCL4 secretion. Nat Med. 2014; 20(11): 1315-20. https://doi.org/10.1038/nm.3707  PMid:25326802      PMCid:PMC4258871
248. Zhao M, Perry JM, Marshall H, et al. Megakaryocytes maintain homeostatic quiescence and promote post-injury regeneration of hematopoietic stem cells. Nat Med. 2014; 20(11): 1321-26.https://doi.org/10.1038/nm.3706   PMid:25326798
249. Chow A, Huggins M, Ahmed J, et al. CD169? macrophages provide a niche promoting erythropoiesis under homeostasis and stress. Nat Med. 2013; 19(4): 429-36. https://doi.org/10.1038/nm.3057  PMid:23502962      PMCid:PMC3983996
250. Ramos P, Casu C, Gardenghi S, et al. Macrophages support pathological erythropoiesis in polycythemia vera and ?-thalassemia. Nat Med. 2013; 19(4): 437-45. https://doi.org/10.1038/nm.3126  PMid:23502961      PMCid:PMC3618568
251. Chow A, Lucas D, Hidalgo A, et al. Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche. J Exp Med. 2011; 208(2): 261-71. https://doi.org/10.1084/jem.20101688   PMid:21282381      PMCid:PMC3039855
252. Christopher MJ, Rao M, Liu F, et al. Expression of the G-CSF receptor in monocytic cells is sufficient to mediate hematopoietic progenitor mobilization by G-CSF in mice. J Exp Med. 2011; 208(2): 251-60. https://doi.org/10.1084/jem.20101700   PMid:21282380      PMCid:PMC3039862
253. Winkler IG, Sims NA, Pettit AR, et al. Bone marrow macrophages maintain hematopoietic stem cell (HSCs) niches and their depletion mobilizes HSCs. Blood. 2010; 116(23): 4815-28.https://doi.org/10.1182/blood-2009-11-253534   PMid:20713966
254. Lucas D, Bruns I, Battista M, et al. Norepinephrine reuptake inhibition promotes mobilization in mice: potential impact to rescue low stem cell yields. Blood. 2012; 119(17): 3962-65.https://doi.org/10.1182/blood-2011-07-367102   PMid:22422821      PMCid:PMC3350363
255. Dutta P, Hoyer FF, Grigoryeva LS, et al. Macrophages retain hematopoietic stem cells in the spleen via VCAM-1. J Exp Med. 2015; 212(4): 497-512. https://doi.org/10.1084/jem.20141642  PMid:25800955      PMCid:PMC4387283
256. Naveiras O, Nardi V, Wenzel PL, et al. Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment. Nature. 2009; 460(7252): 259-63. https://doi.org/10.1038/nature08099  PMid:19516257      PMCid:PMC2831539
257. Miyamoto K, Yoshida S, Kawasumi M, et al. Osteoclasts are dispensable for hematopoietic stem cell maintenance and mobilization. J Exp Med. 2011; 208(11): 2175-81.https://doi.org/10.1084/jem.20101890   PMid:22006978      PMCid:PMC3201203
258. Fujisaki J, Wu J, Carlson AL, et al. In vivo imaging of Treg cells providing immune privilege to the haematopoietic stem-cell niche. Nature. 2011; 474(7350): 216-19.https://doi.org/10.1038/nature10160   PMid:21654805      PMCid:PMC3725645
259. Istvanffy R, Kroger M, Eckl C, et al. Stromal pleiotrophin regulates repopulation behavior of hematopoietic stem cells. Blood. 2011; 118(10): 2712-22. https://doi.org/10.1182/blood-2010-05-287235  PMid:21791434
260. Ghiaur G, Yegnasubramanian S, Perkins B, et al. Regulation of human hematopoietic stem cell self-renewal by the microenvironment’s control of retinoic acid signaling. Proc Natl Acad Sci USA. 2013; 110(40): 16121-126. https://doi.org/10.1073/pnas.1305937110   PMid:24043786      PMCid:PMC3791732
261. Spoorendonk KM, Peterson-Maduro J, Renn J, et al. Retinoic acid and Cyp26b1 are critical regulators of osteogenesis in the axial skeleton. Development. 2008; 135(22): 3765-74.https://doi.org/10.1242/dev.024034   PMid:18927155

Nikolskaya EI, Butenko GM. Structural-functional organisation of the bone marrow hematopoietic stem cells niches. Cell and Organ Transplantology. 2016; 4(1):100-117. doi: 10.22494/COT.V4I1.9

 

Creative Commons License
Is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.