Hematopoietic stem cells (HSCs) play a key role in hematopoietic system that functions mainly in homeostasis and immune response. HSCs transplantation has been applied for the treatment of several diseases. However, HSCs persist in the small quantity within the body, mostly in the quiescent state. Understanding the basic knowledge of HSCs is useful for stem cell biology research and therapeutic medicine development. Thus, this paper emphasizes on HSC origin, source, development, the niche, and signaling pathways which support HSC maintenance and balance between self-renewal and proliferation which will be useful for the advancement of HSC expansion and transplantation in the future. 1. Introduction Hematopoietic stem cells (HSC) are adult stem cells that contain the potentiality in self-renew and differentiation into specialized blood cells that function in some biological activities: control homeostasis balance, immune function, and response to microorganisms and inflammation. HSCs can also differentiate into other specialized cell or so called plasticity such as adipocytes [1], cardiomyocytes [2], endothelial cells [3], fibroblasts/myofibroblasts [4], liver cells [5, 6], osteochondrocytes [7, 8], and pancreatic cells [9]. Most HSCs are in quiescent state within the niches that maintain HSC pool and will respond to the signals after the balance of blood cells or HSC pool is disturbed from either intrinsic or extrinsic stimuli. In addition, HSCs have been studied extensively, especially, for the therapeutic purposes in the treatment of blood diseases, inherited blood disorders, and autoimmune diseases. Nonetheless, advanced development in this field needs knowledge in the biological studies as a background in performing strategy and maintaining of HSCs. Thus, HSC source, origin, niches for HSC pool, and signaling pathways, essential for the regulation of HSCs, will be discussed in this review. 2. HSCs Origin and Development In the hematopoietic system, the discovery of HSCs has shed the light on stem cell biology studies including connection to other adult stem cells through the basic concepts of differentiation, multipotentiality, and self-renewal. In the early period of those discoveries, lethally irradiated animals were found to be rescued by spleen cells or marrow cells [17, 18]. After mouse bone marrow cells were transplanted into irradiated mice, the clonogenic mixed colony of hematopoietic cells (often composed of granulocyte/megakaryocyte and erythroid precursors) were formed within the spleen, which these colonies were then termed
References
[1]
Y. Sera, A. C. LaRue, O. Moussa et al., “Hematopoietic stem cell origin of adipocytes,” Experimental Hematology, vol. 37, no. 9, pp. 1108.e4–1120.e4, 2009.
[2]
M. Pozzobon, S. Bollini, L. Iop et al., “Human bone marrow-derived CD133+ cells delivered to a collagen patch on cryoinjured rat heart promote angiogenesis and arteriogenesis,” Cell Transplantation, vol. 19, no. 10, pp. 1247–1260, 2010.
[3]
N. Elkhafif, H. El Baz, O. Hammam et al., “CD133+ human umbilical cord blood stem cells enhance angiogenesis in experimental chronic hepatic fibrosis,” Acta Pathologica, Microbiologica et Immunologica, vol. 119, no. 1, pp. 66–75, 2011.
[4]
Y. Ebihara, M. Masuya, A. C. LaRue et al., “Hematopoietic origins of fibroblasts: II. In vitro studies of fibroblasts, CFU-F, and fibrocytes,” Experimental Hematology, vol. 34, no. 2, pp. 219–229, 2006.
[5]
S. Khurana and A. Mukhopadhyay, “In vitro transdifferentiation of adult hematopoietic stem cells: an alternative source of engraftable hepatocytes,” Journal of Hepatology, vol. 49, no. 6, pp. 998–1007, 2008.
[6]
S. Sellamuthu, R. Manikandan, R. Thiagarajan et al., “In vitro trans-differentiation of human umbilical cord derived hematopoietic stem cells into hepatocyte like cells using combination of growth factors for cell based therapy,” Cytotechnology, vol. 63, no. 3, pp. 259–268, 2011.
[7]
M. Dominici, C. Pritchard, J. E. Garlits, T. J. Hofmann, D. A. Persons, and E. M. Horwitz, “Hematopoietic cells and osteoblasts are derived from a common marrow progenitor after bone marrow transplantation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 32, pp. 11761–11766, 2004.
[8]
M. Mehrotra, M. Rosol, M. Ogawa, and A. C. LaRue, “Amelioration of a mouse model of osteogenesis imperfecta with hematopoietic stem cell transplantation: microcomputed tomography studies,” Experimental Hematology, vol. 38, no. 7, pp. 593–602, 2010.
[9]
H. Minamiguchi, F. Ishikawa, P. A. Fleming et al., “Transplanted human cord blood cells generate amylase-producing pancreatic acinar cells in engrafted mice,” Pancreas, vol. 36, no. 2, pp. e30–e35, 2008.
[10]
S. Coskun and K. K. Hirschi, “Establishment and regulation of the HSC niche: roles of osteoblastic and vascular compartments,” Birth Defects Research C, vol. 90, no. 4, pp. 229–242, 2010.
[11]
C. Gekas, K. E. Rhodes, B. van Handel, A. Chhabra, M. Ueno, and H. K. A. Mikkola, “Hematopoietic stem cell development in the placenta,” International Journal of Developmental Biology, vol. 54, no. 6-7, pp. 1089–1098, 2010.
[12]
T. Nagasawa, Y. Omatsu, and T. Sugiyama, “Control of hematopoietic stem cells by the bone marrow stromal niche: the role of reticular cells,” Trends in Immunology, vol. 32, no. 7, pp. 315–320, 2011.
[13]
J. Seita and I. L. Weissman, “Hematopoietic stem cell: self-renewal versus differentiation,” Wiley Interdisciplinary Reviews, vol. 2, no. 6, pp. 640–653, 2010.
[14]
F. S. Chou and J. C. Mulloy, “The thrombopoietin/MPL pathway in hematopoiesis and leukemogenesis,” Journal of Cellular Biochemistry, vol. 112, no. 6, pp. 1491–1498, 2011.
[15]
A. E. Geddis, “Megakaryopoiesis,” Seminars in Hematology, vol. 47, no. 3, pp. 212–219, 2010.
[16]
M. Katoh and M. Katoh, “WNT signaling pathway and stem cell signaling network,” Clinical Cancer Research, vol. 13, no. 14, pp. 4042–4045, 2007.
[17]
L. O. Jacobson, E. L. Simmons, E. K. Marks, and J. H. Eldredge, “Recovery from radiation injury,” Science, vol. 113, no. 2940, pp. 510–511, 1951.
[18]
E. Lorenz, D. Uphoff, T. R. REID, and E. Shelton, “Modification of irradiation injury in mice and guinea pigs by bone marrow injections,” Journal of the National Cancer Institute, vol. 12, no. 1, pp. 197–201, 1951.
[19]
J. E. Till and E. A. Mc, “A direct measurement of the radiation sensitivity of normal mouse bone marrow cells,” Radiation Research, vol. 14, pp. 213–222, 1961.
[20]
L. Siminovitch, E. A. Mcculloch, and J. E. Till, “The distribution of colony-forming cells among spleen colonies,” Journal of Cellular Physiology, vol. 62, pp. 327–336, 1963.
[21]
R. Schofield, “The relationship between the spleen colony-forming cell and the haemopoietic stem cell. A hypothesis,” Blood Cells, vol. 4, no. 1-2, pp. 7–25, 1978.
[22]
M. A. Moore and D. Metcalf, “Ontogeny of the haemopoietic system: yolk sac origin of in vivo and in vitro colony forming cells in the developing mouse embryo,” British Journal of Haematology, vol. 18, no. 3, pp. 279–296, 1970.
[23]
B. M. Zeigler, D. Sugiyama, M. Chen, Y. Guo, K. M. Downs, and N. A. Speck, “The allantois and chorion, when isolated before circulation or chorio-allantoic fusion, have hematopoietic potential,” Development, vol. 133, no. 21, pp. 4183–4192, 2006.
[24]
A. Medvinsky and E. Dzierzak, “Definitive hematopoiesis is autonomously initiated by the AGM region,” Cell, vol. 86, no. 6, pp. 897–906, 1996.
[25]
A. M. Müller, A. Medvinsky, J. Strouboulis, F. Grosveld, and E. Dzierzak, “Development of hematopoietic stem cell activity in the mouse embryo,” Immunity, vol. 1, no. 4, pp. 291–301, 1994.
[26]
M. F. T. R. de Bruijn, N. A. Speck, M. C. E. Peeters, and E. Dzierzak, “Definitive hematopoietic stem cells first develop within the major arterial regions of the mouse embryo,” The EMBO Journal, vol. 19, no. 11, pp. 2465–2474, 2000.
[27]
A. Huyhn, M. Dommergues, B. Izac et al., “Characterization of hematopoietic progenitors from human yolk sacs and embryos,” Blood, vol. 86, no. 12, pp. 4474–4485, 1995.
[28]
M. C. Labastie, F. Cortés, P. H. Roméo, C. Dulac, and B. Péault, “Molecular identity of hematopoietic precursor cells emerging in the human embryo,” Blood, vol. 92, no. 10, pp. 3624–3635, 1998.
[29]
M. Tavian, L. Coulombel, D. Luton, H. S. Clemente, F. Dieterlen-Lièvre, and B. Péault, “Aorta-associated CD34+ hematopoietic cells in the early human embryo,” Blood, vol. 87, no. 1, pp. 67–72, 1996.
[30]
M. Tavian, C. Robin, L. Coulombel, and B. Péault, “The human embryo, but not its yolk sac, generates lympho-myeloid stem cells: mapping multipotent hematopoietic cell fate in intraembryonic mesoderm,” Immunity, vol. 15, no. 3, pp. 487–495, 2001.
[31]
M. J. Chen, T. Yokomizo, B. M. Zeigler, E. Dzierzak, and N. A. Speck, “Runx1 is required for the endothelial to haematopoietic cell transition but not thereafter,” Nature, vol. 457, no. 7231, pp. 887–891, 2009.
[32]
M. F. T. R. de Bruijn, X. Ma, C. Robin, K. Ottersbach, M. J. Sanchez, and E. Dzierzak, “Hematopoietic stem cells localize to the endothelial cell layer in the midgestation mouse aorta,” Immunity, vol. 16, no. 5, pp. 673–683, 2002.
[33]
E. Taylor, S. Taoudi, and A. Medvinsky, “Hematopoietic stem cell activity in the aorta-gonad-mesonephros region enhances after mid-day 11 of mouse development,” International Journal of Developmental Biology, vol. 54, no. 6-7, pp. 1055–1060, 2010.
[34]
A. Bárcena, M. Kapidzic, M. O. Muench et al., “The human placenta is a hematopoietic organ during the embryonic and fetal periods of development,” Developmental Biology, vol. 327, no. 1, pp. 24–33, 2009.
[35]
C. Robin, K. Bollerot, S. Mendes et al., “Human placenta is a potent hematopoietic niche containing hematopoietic stem and progenitor cells throughout development,” Cell Stem Cell, vol. 5, no. 4, pp. 385–395, 2009.
[36]
J. C. Cross, “How to make a placenta: mechanisms of trophoblast cell differentiation in mice—a review,” Placenta, vol. 26, supplement 1, pp. S3–S9, 2005.
[37]
P. Georgiades, A. C. Fergyson-Smith, and G. J. Burton, “Comparative developmental anatomy of the murine and human definitive placentae,” Placenta, vol. 23, no. 1, pp. 3–19, 2002.
[38]
B. Cox, M. Kotlyar, A. I. Evangelou et al., “Comparative systems biology of human and mouse as a tool to guide the modeling of human placental pathology,” Molecular Systems Biology, vol. 5, article 279, 2009.
[39]
J. Rossant and J. C. Cross, “Placental development: lessons from mouse mutants,” Nature Reviews Genetics, vol. 2, no. 7, pp. 538–548, 2001.
[40]
C. Corbel, J. Salaün, P. Belo-Diabangouaya, and F. Dieterlen-Lièvre, “Hematopoietic potential of the pre-fusion allantois,” Developmental Biology, vol. 301, no. 2, pp. 478–488, 2007.
[41]
K. E. Rhodes, C. Gekas, Y. Wang et al., “The emergence of hematopoietic stem cells isInitiated in the placental vasculature in the absence of circulation,” Cell Stem Cell, vol. 2, no. 3, pp. 252–263, 2008.
[42]
P. D. F. Murray, “The development in vitro of the blood of the early chick embryo,” Proceedings of the Royal Society, vol. 111, no. 773, pp. 497–521, 1932.
[43]
T. Jaffredo, R. Gautier, A. Eichmann, and F. Dieterlen-Lièvre, “Intraaortic hemopoietic cells are derived from endothelial cells during ontogeny,” Development, vol. 125, no. 22, pp. 4575–4583, 1998.
[44]
S. I. Nishikawa, S. Nishikawa, H. Kawamoto et al., “In vitro generation of lymphohematopoietic cells from endothelial cells purified from murine embryos,” Immunity, vol. 8, no. 6, pp. 761–769, 1998.
[45]
H. M. Eilken, S. I. Nishikawa, and T. Schroeder, “Continuous single-cell imaging of blood generation from haemogenic endothelium,” Nature, vol. 457, no. 7231, pp. 896–900, 2009.
[46]
J. C. Boisset, W. Van Cappellen, C. Andrieu-Soler, N. Galjart, E. Dzierzak, and C. Robin, “In vivo imaging of haematopoietic cells emerging from the mouse aortic endothelium,” Nature, vol. 464, no. 7285, pp. 116–120, 2010.
[47]
E. Oberlin, B. E. Hafny, L. Petit-Cocault, and M. Souyri, “Definitive human and mouse hematopoiesis originates from the embryonic endothelium: a new class of HSCs based on VE-cadherin expression,” International Journal of Developmental Biology, vol. 54, no. 6-7, pp. 1165–1173, 2010.
[48]
T. Ara, K. Tokoyoda, T. Sugiyama, T. Egawa, K. Kawabata, and T. Nagasawa, “Long-term hematopoietic stem cells require stromal cell-derived factor-1 for colonizing bone marrow during ontogeny,” Immunity, vol. 19, no. 2, pp. 257–267, 2003.
[49]
Y. Guo, G. Hangoc, H. Bian, L. M. Pelus, and H. E. Broxmeyer, “SDF-1/CXCL12 enhances survival and chemotaxis of murine embryonic stem cells and production of primitive and definitive hematopoietic progenitor cells,” Stem Cells, vol. 23, no. 9, pp. 1324–1332, 2005.
[50]
T. Xie and A. C. Spradling, “decapentaplegic is essential for the maintenance and division of germline stem cells in the Drosophila ovary,” Cell, vol. 94, no. 2, pp. 251–260, 1998.
[51]
S. K. Nilsson, P. J. Simmons, and I. Bertoncello, “Hemopoietic stem cell engraftment,” Experimental Hematology, vol. 34, no. 2, pp. 123–129, 2006.
[52]
S. Basu, N. T. Ray, S. J. Atkinson, and H. E. Broxmeyer, “Protein phosphatase 2A plays an important role in stromal cell-derived factor-1/CXC chemokine ligand 12-mediated migration and adhesion of CD34+ cells,” Journal of Immunology, vol. 179, no. 5, pp. 3075–3085, 2007.
[53]
C. Lo Celso, H. E. Fleming, J. W. Wu et al., “Live-animal tracking of individual haematopoietic stem/progenitor cells in their niche,” Nature, vol. 457, no. 7225, pp. 92–96, 2009.
[54]
Y. Xie, T. Yin, W. Wiegraebe et al., “Detection of functional haematopoietic stem cell niche using real-time imaging,” Nature, vol. 457, no. 7225, pp. 97–101, 2009.
[55]
Y. Jung, J. Song, Y. Shiozawa et al., “Hematopoietic stem cells regulate mesenchymal stromal cell induction into osteoblasts thereby participating in the formation of the stem cell niche,” Stem Cells, vol. 26, no. 8, pp. 2042–2051, 2008.
[56]
L. M. Calvi, G. B. Adams, K. W. Weibrecht et al., “Osteoblastic cells regulate the haematopoietic stem cell niche,” Nature, vol. 425, no. 6960, pp. 841–846, 2003.
[57]
J. M. Weber, S. R. Forsythe, C. A. Christianson et al., “Parathyroid hormone stimulates expression of the Notch ligand Jagged1 in osteoblastic cells,” Bone, vol. 39, no. 3, pp. 485–493, 2006.
[58]
B. R. Chitteti, Y. H. Cheng, B. Poteat et al., “Impact of interactions of cellular components of the bone marrow microenvironment on hematopoietic stem and progenitor cell function,” Blood, vol. 115, no. 16, pp. 3239–3248, 2010.
[59]
F. Arai, A. Hirao, M. Ohmura et al., “Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche,” Cell, vol. 118, no. 2, pp. 149–161, 2004.
[60]
R. S. Taichman, “Blood and bone: two tissues whose fates are intertwined to create the hematopoietic stem-cell niche,” Blood, vol. 105, no. 7, pp. 2631–2639, 2005.
[61]
S. Stier, Y. Ko, R. Forkert et al., “Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size,” Journal of Experimental Medicine, vol. 201, no. 11, pp. 1781–1791, 2005.
[62]
N. D. Staudt, W. K. Aicher, H. Kalbacher et al., “Cathepsin X is secreted by human osteoblasts, digests CXCL-12 and impairs adhesion of hematopoietic stem and progenitor cells to osteoblasts,” Haematologica, vol. 95, no. 9, pp. 1452–1460, 2010.
[63]
A. P. D. N. de Barros, C. M. Takiya, L. R. Garzoni et al., “Osteoblasts and bone marrow mesenchymal stromal cells control hematopoietic stem cell migration and proliferation in 3D in vitro model,” PLoS ONE, vol. 5, no. 2, Article ID e9093, 2010.
[64]
Y. Nakamura, F. Arai, H. Iwasaki et al., “Isolation and characterization of endosteal niche cell populations that regulate hematopoietic stem cells,” Blood, vol. 116, no. 9, pp. 1422–1432, 2010.
[65]
J. Zhang, C. Niu, L. Ye et al., “Identification of the haematopoietic stem cell niche and control of the niche size,” Nature, vol. 425, no. 6960, pp. 836–841, 2003.
[66]
J. Zhu, R. Garrett, Y. Jung, et al., “Osteoblasts support B-lymphocyte commitment and differentiation from hematopoietic stem cell,” Blood, vol. 109, no. 9, pp. 3706–3712, 2007.
[67]
D. Visnjic, Z. Kalajzic, D. W. Rowe, V. Katavic, J. Lorenzo, and H. L. Aguila, “Hematopoiesis is severely altered in mice with an induced osteoblast deficiency,” Blood, vol. 103, no. 9, pp. 3258–3264, 2004.
[68]
M. J. Kiel, G. L. Radice, and S. J. Morrison, “Lack of evidence that hematopoietic stem cells depend on N-cadherin-mediated adhesion to osteoblasts for their maintenance,” Cell Stem Cell, vol. 1, no. 2, pp. 204–217, 2007.
[69]
Y. D. Ma, C. Park, H. Zhao 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, vol. 114, no. 20, pp. 4402–4410, 2009.
[70]
M. J. Kiel, M. Acar, G. L. Radice, and S. J. Morrison, “Hematopoietic stem cells do not depend on N-cadherin to regulate their maintenance,” Cell Stem Cell, vol. 4, no. 2, pp. 170–179, 2009.
[71]
B. Li, A. S. Bailey, S. Jiang, B. Liu, D. C. Goldman, and W. H. Fleming, “Endothelial cells mediate the regeneration of hematopoietic stem cells,” Stem Cell Research, vol. 4, no. 1, pp. 17–24, 2010.
[72]
A. B. Salter, S. K. Meadows, G. G. Muramoto et al., “Endothelial progenitor cell infusion induces hematopoietic stem cell reconstitution in vivo,” Blood, vol. 113, no. 9, pp. 2104–2107, 2009.
[73]
H. Kobayashi, J. M. Butler, R. O'Donnell et al., “Angiocrine factors from Akt-activated endothelial cells balance self-renewal and differentiation of haematopoietic stem cells,” Nature Cell Biology, vol. 12, no. 11, pp. 1046–1056, 2010.
[74]
M. G. Kharas, R. Okabe, J. J. Ganis et al., “Constitutively active AKT depletes hematopoietic stem cells and induces leukemia in mice,” Blood, vol. 115, no. 7, pp. 1406–1415, 2010.
[75]
A. T. Hooper, J. M. Butler, D. J. Nolan et al., “Engraftment and reconstitution of hematopoiesis is dependent on VEGFR2-mediated regeneration of sinusoidal endothelial cells,” Cell Stem Cell, vol. 4, no. 3, pp. 263–274, 2009.
[76]
J. M. Butler, D. J. Nolan, E. L. Vertes et al., “Endothelial cells are essential for the self-renewal and repopulation of notch-dependent hematopoietic stem cells,” Cell Stem Cell, vol. 6, no. 3, pp. 251–264, 2010.
[77]
T. Sugiyama, H. Kohara, M. Noda, and T. Nagasawa, “Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches,” Immunity, vol. 25, no. 6, pp. 977–988, 2006.
[78]
Y. Nie, Y. C. Han, and Y. R. Zou, “CXCR4 is required for the quiescence of primitive hematopoietic cells,” Journal of Experimental Medicine, vol. 205, no. 4, pp. 777–783, 2008.
[79]
M. Noda, Y. Omatsu, T. Sugiyama, S. Oishi, N. Fujii, and T. Nagasawa, “CXCL12-CXCR4 chemokine signaling is essential for NK-cell development in adult mice,” Blood, vol. 117, no. 2, pp. 451–458, 2011.
[80]
H. Kohara, Y. Omatsu, T. Sugiyama, M. Noda, N. Fujii, and T. Nagasawa, “Development of plasmacytoid dendritic cells in bone marrow stromal cell niches requires CXCL12-CXCR4 chemokine signaling,” Blood, vol. 110, no. 13, pp. 4153–4160, 2007.
[81]
T. Nagasawa, “Microenvironmental niches in the bone marrow required for B-cell development,” Nature Reviews Immunology, vol. 6, no. 2, pp. 107–116, 2006.
[82]
Y. Omatsu, T. Sugiyama, H. Kohara et al., “The essential functions of adipo-osteogenic progenitors as the hematopoietic stem and progenitor cell niche,” Immunity, vol. 33, no. 3, pp. 387–399, 2010.
[83]
B. Sacchetti, A. Funari, S. Michienzi et al., “Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment,” Cell, vol. 131, no. 2, pp. 324–336, 2007.
[84]
D. Traver, K. Akashi, M. Manz et al., “Development of CD8α-positive dendritic cells from a common myeloid progenitor,” Science, vol. 290, no. 5499, pp. 2152–2154, 2000.
[85]
M. G. Manz, D. Traver, K. Akashi et al., “Dendritic cell development from common myeloid progenitors,” Annals of the New York Academy of Sciences, vol. 938, pp. 167–174, 2001.
[86]
M. G. Manz, D. Traver, T. Miyamoto, I. L. Weissman, and K. Akashi, “Dendritic cell potentials of early lymphoid and myeloid progenitors,” Blood, vol. 97, no. 11, pp. 3333–3341, 2001.
[87]
R. Doyonnas, D. B. Kershaw, C. Duhme et al., “Anuria, omphalocele, and perinatal lethality in mice lacking the CD34-related protein podocalyxin,” Journal of Experimental Medicine, vol. 194, no. 1, pp. 13–27, 2001.
[88]
C. Sassetti, A. Van Zante, and S. D. Rosen, “Identification of endoglycan, a member of the CD34/podocalyxin family of sialomucins,” Journal of Biological Chemistry, vol. 275, no. 12, pp. 9001–9010, 2000.
[89]
C. Sassetti, K. Tangemann, M. S. Singer, D. B. Kershaw, and S. D. Rosen, “Identification of Podocalyxin-like protein as a high endothelial venule ligand for L-selectin: parallels to CD34,” Journal of Experimental Medicine, vol. 187, no. 12, pp. 1965–1975, 1998.
[90]
P. Pranke, J. Hendrikx, G. Debnath et al., “Immunophenotype of hematopoietic stem cells from placental/umbilical cord blood after culture,” Brazilian Journal of Medical and Biological Research, vol. 38, no. 12, pp. 1775–1789, 2005.
[91]
J. P. Hossle, R. A. Seger, and D. Steinhoff, “Gene therapy of hematopoietic stem cells: strategies for improvement,” News in Physiological Sciences, vol. 17, no. 3, pp. 87–92, 2002.
[92]
D. S. Krause, M. J. Fackler, C. I. Civin, and W. S. May, “CD34: structure, biology, and clinical utility,” Blood, vol. 87, no. 1, pp. 1–13, 1996.
[93]
C. M. Baum, I. L. Weissman, A. S. Tsukamoto, A. M. Buckle, and B. Peault, “Isolation of a candidate human hematopoietic stem-cell population,” Proceedings of the National Academy of Sciences of the United States of America, vol. 89, no. 7, pp. 2804–2808, 1992.
[94]
M. Bhatia, J. C. Y. Wang, U. Kapp, D. Bonnet, and J. E. Dick, “Purification of primitive human hematopoietic cells capable of repopulating immune-deficient mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 10, pp. 5320–5325, 1997.
[95]
Q. L. Hao, A. J. Shah, F. T. Thiemann, E. M. Smogorzewska, and G. M. Crooks, “A functional comparison of CD34+CD38- cells in cord blood and bone marrow,” Blood, vol. 86, no. 10, pp. 3745–3753, 1995.
[96]
H. Mayani, W. Dragowska, and P. M. Lansdorp, “Characterization of functionally distinct subpopulations of CD34+ cord blood cells in serum-free long-term cultures supplemented with hematopoietic cytokines,” Blood, vol. 82, no. 9, pp. 2664–2672, 1993.
[97]
R. Majeti, C. Y. Park, and I. L. Weissman, “Identification of a hierarchy of multipotent hematopoietic progenitors in human cord blood,” Cell Stem Cell, vol. 1, no. 6, pp. 635–645, 2007.
[98]
F. Notta, S. Doulatov, E. Laurenti, A. Poeppl, I. Jurisica, and J. E. Dick, “Isolation of single human hematopoietic stem cells capable of long-term multilineage engraftment,” Science, vol. 333, no. 6039, pp. 218–221, 2011.
[99]
W. H. Fleming, E. J. Alpern, N. Uchida, K. Ikuta, G. J. Spangrude, and I. L. Weissman, “Functional heterogeneity is associated with the cell cycle status of murine hematopoietic stem cells,” Journal of Cell Biology, vol. 122, no. 4, pp. 897–902, 1993.
[100]
M. Z. Ratajczak, E. Zuba-Surma, M. Kucia, R. Reca, W. Wojakowski, and J. Ratajczak, “The pleiotropic effects of the SDF-1-CXCR4 axis in organogenesis, regeneration and tumorigenesis,” Leukemia, vol. 20, no. 11, pp. 1915–1924, 2006.
[101]
M. Shirozu, T. Nakano, J. Inazawa et al., “Structure and chromosomal localization of the human stromal cell-derived factor 1 (SDF1) gene,” Genomics, vol. 28, no. 3, pp. 495–500, 1995.
[102]
M. Gleichmann, C. Gillen, M. Czardybon et al., “Cloning and characterization of SDF-1γ, a novel SDF-1 chemokine transcript with developmentally regulated expression in the nervous system,” European Journal of Neuroscience, vol. 12, no. 6, pp. 1857–1866, 2000.
[103]
L. Yu, J. Cecil, S. B. Peng et al., “Identification and expression of novel isoforms of human stromal cell-derived factor 1,” Gene, vol. 374, no. 1-2, pp. 174–179, 2006.
[104]
K. Balabanian, B. Lagane, S. Infantino et al., “The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes,” Journal of Biological Chemistry, vol. 280, no. 42, pp. 35760–35766, 2005.
[105]
B. Moepps, M. Braun, K. Knopfle, et al., “Characterization of a Xenopus laevis CXC chemokine receptor 4: implications for hematopoietic cell development in the vertebrate embryo,” European Journal of Immunology, vol. 30, no. 10, pp. 2924–2934, 2000.
[106]
M. Braun, M. Wunderlin, K. Spieth, W. Kn？chel, P. Gierschik, and B. Moepps, “Xenopus laevis stromal cell-derived factor 1: conservation of structure and function during vertebrate development,” Journal of Immunology, vol. 168, no. 5, pp. 2340–2347, 2002.
[107]
H. Zheng, G. Fu, T. Dai, and H. Huang, “Migration of endothelial progenitor cells mediated by stromal cell-derived factor-1α/CXCR4 via PI3K/Akt/eNOS signal transduction pathway,” Journal of Cardiovascular Pharmacology, vol. 50, no. 3, pp. 274–280, 2007.
[108]
D. J. Ceradini, A. R. Kulkarni, M. J. Callaghan et al., “Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1,” Nature Medicine, vol. 10, no. 8, pp. 858–864, 2004.
[109]
Y. Yang, G. Tang, J. Yan et al., “Cellular and molecular mechanism regulating blood flow recovery in acute versus gradual femoral artery occlusion are distinct in the mouse,” Journal of Vascular Surgery, vol. 48, no. 6, pp. 1546–1558, 2008.
[110]
J. I. Yamaguchi, K. F. Kusano, O. Masuo et al., “Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cell recruitment for ischemic neovascularization,” Circulation, vol. 107, no. 9, pp. 1322–1328, 2003.
[111]
H. Liu, S. Liu, Y. Li, et al., “The role of SDF-1-CXCR4/CXCR7 axis in the therapeutic effects of hypoxia-preconditioned mesenchymal stem cells for renal ischemia/reperfusion injury,” PLoS One, vol. 7, no. 4, Article ID e34608, 2012.
[112]
B. Heissig, K. Hattori, S. Dias et al., “Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of Kit-ligand,” Cell, vol. 109, no. 5, pp. 625–637, 2002.
[113]
Y. S. Tzeng, H. Li, Y. L. Kang, W. G. Chen, W. Cheng, and D. M. Lai, “Loss of Cxcl12/Sdf-1 in adult mice decreases the quiescent state of hematopoietic stem/progenitor cells and alters the pattern of hematopoietic regeneration after myelosuppression,” Blood, vol. 117, no. 2, pp. 429–439, 2011.
[114]
A. H. Reddi and A. Reddi, “Bone morphogenetic proteins (BMPs): from morphogens to metabologens,” Cytokine and Growth Factor Reviews, vol. 20, no. 5-6, pp. 341–342, 2009.
[115]
R. Garimella, S. E. Tague, J. Zhang et al., “Expression and synthesis of bone morphogenetic proteins by osteoclasts: a possible path to anabolic bone remodeling,” Journal of Histochemistry and Cytochemistry, vol. 56, no. 6, pp. 569–577, 2008.
[116]
D. C. Goldman, A. S. Bailey, D. L. Pfaffle, A. Al Masri, J. L. Christian, and W. H. Fleming, “BMP4 regulates the hematopoietic stem cell niche,” Blood, vol. 114, no. 20, pp. 4393–4401, 2009.
[117]
C. Durand, C. Robin, K. Bollerot, M. H. Baron, K. Ottersbach, and E. Dzierzak, “Embryonic stromal clones reveal developmental regulators of definitive hematopoietic stem cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 52, pp. 20838–20843, 2007.
[118]
M. Bhatia, D. Bonnet, D. Wu et al., “Bone morphogenetic proteins regulate the developmental program of human hematopoietic stem cells,” Journal of Experimental Medicine, vol. 189, no. 7, pp. 1139–1148, 1999.
[119]
V. C. Broudy and K. Kaushansky, “Thrombopoietin, the c-mpl ligand, is a major regulator of platelet production,” Journal of Leukocyte Biology, vol. 57, no. 5, pp. 719–725, 1995.
[120]
N. Debili, F. Wendling, D. Cosman et al., “The MpI receptor is expressed in the megakaryocytic lineage from late progenitors to platelets,” Blood, vol. 85, no. 2, pp. 391–401, 1995.
[121]
O. Livnah, E. A. Stura, S. A. Middleton, D. L. Johnson, L. K. Jolliffe, and I. A. Wilson, “Crystallographic evidence for preformed dimers of erythropoietin receptor before ligand activation,” Science, vol. 283, no. 5404, pp. 987–990, 1999.
[122]
J. G. Drachman and K. Kaushansky, “Dissecting the thrombopoietin receptor: functional elements of the Mpl cytoplasmic domain,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 6, pp. 2350–2355, 1997.
[123]
B. A. Witthuhn, F. W. Quelle, O. Silvennoinen et al., “JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin,” Cell, vol. 74, no. 2, pp. 227–236, 1993.
[124]
P. J. Tortolani, J. A. Johnston, C. M. Bacon et al., “Thrombopoietin induces tyrosine phosphorylation and activation of the Janus kinase, JAK2,” Blood, vol. 85, no. 12, pp. 3444–3451, 1995.
[125]
H. Yoshihara, F. Arai, K. Hosokawa et al., “Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche,” Cell Stem Cell, vol. 1, no. 6, pp. 685–697, 2007.
[126]
H. Qian, N. Buza-Vidas, C. D. Hyland et al., “Critical role of thrombopoietin in maintaining adult quiescent hematopoietic stem cells,” Cell Stem Cell, vol. 1, no. 6, pp. 671–684, 2007.
[127]
A. Bersenev, C. Wu, J. Balcerek, and W. Tong, “Lnk controls mouse hematopoietic stem cell self-renewal and quiescence through direct interactions with JAK2,” Journal of Clinical Investigation, vol. 118, no. 8, pp. 2832–2844, 2008.
[128]
A. Rongvaux, T. Willinger, H. Takizawa et al., “Human thrombopoietin knockin mice efficiently support human hematopoiesis in vivo,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 6, pp. 2378–2383, 2011.
[129]
Y. Gomei, Y. Nakamura, H. Yoshihara et al., “Functional differences between two Tie2 ligands, angiopoietin-1 and -2, in regulation of adult bone marrow hematopoietic stem cells,” Experimental Hematology, vol. 38, no. 2, pp. 82.e1–89.e1, 2010.
[130]
J. J. Trowbridge, M. P. Scott, and M. Bhatia, “Hedgehog modulates cell cycle regulators in stem cells to control hematopoietic regeneration,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 38, pp. 14134–14139, 2006.
[131]
C. Zhao, A. Chen, C. H. Jamieson et al., “Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia,” Nature, vol. 458, no. 7239, pp. 776–779, 2009.
[132]
A. Merchant, G. Joseph, Q. Wang, S. Brennan, and W. Matsui, “Gli1 regulates the proliferation and differentiation of HSCs and myeloid progenitors,” Blood, vol. 115, no. 12, pp. 2391–2396, 2010.
[133]
I. Hofmann, E. H. Stover, D. E. Cullen et al., “Hedgehog signaling is dispensable for adult murine hematopoietic stem cell function and hematopoiesis,” Cell Stem Cell, vol. 4, no. 6, pp. 559–567, 2009.
[134]
J. Gao, S. Graves, U. Koch et al., “Hedgehog signaling is dispensable for adult hematopoietic stem cell function,” Cell Stem Cell, vol. 4, no. 6, pp. 548–558, 2009.
[135]
S. Artavanis-Tsakonas, M. D. Rand, and R. J. Lake, “Notch signaling: cell fate control and signal integration in development,” Science, vol. 284, no. 5415, pp. 770–776, 1999.
[136]
G. L. Lin and K. D. Hankenson, “Integration of BMP, Wnt, and Notch signaling pathways in osteoblast differentiation,” Journal of Cellular Biochemistry, vol. 112, no. 12, pp. 3491–3501, 2011.
[137]
P. Ranganathan, K. L. Weaver, and A. J. Capobianco, “Notch signalling in solid tumours: a little bit of everything but not all the time,” Nature Reviews Cancer, vol. 11, no. 5, pp. 338–351, 2011.
[138]
K. Ohishi, B. Varnum-Finney, and I. D. Bernstein, “Delta-1 enhances marrow and thymus repopulating ability of human CD34+CD38- cord blood cells,” Journal of Clinical Investigation, vol. 110, no. 8, pp. 1165–1174, 2002.
[139]
B. Varnum-Finney, L. M. Halasz, M. Sun, T. Gridley, F. Radtke, and I. D. Bernstein, “Notch2 governs the rate of generation of mouse long- and short-term repopulating stem cells,” Journal of Clinical Investigation, vol. 121, no. 3, pp. 1207–1216, 2011.
[140]
B. Varnum-Finney, C. Brashem-Stein, and I. D. Bernstein, “Combined effects of Notch signaling and cytokines induce a multiple log increase in precursors with lymphoid and myeloid reconstituting ability,” Blood, vol. 101, no. 5, pp. 1784–1789, 2003.
[141]
S. Stier, T. Cheng, D. Dombkowski, N. Carlesso, and D. T. Scadden, “Notch1 activation increases hematopoietic stem cell self-renewal in vivo and favors lymphoid over myeloid lineage outcome,” Blood, vol. 99, no. 7, pp. 2369–2378, 2002.
[142]
J. M. Rowlinson and M. Gering, “Hey2 acts upstream of Notch in hematopoietic stem cell specification in zebrafish embryos,” Blood, vol. 116, no. 12, pp. 2046–2056, 2010.
[143]
I. Maillard, U. Koch, A. Dumortier et al., “Canonical notch signaling is dispensable for theMaintenance of adult hematopoietic stem cells,” Cell Stem Cell, vol. 2, no. 4, pp. 356–366, 2008.
[144]
S. J. C. Mancini, N. Mantei, A. Dumortier, U. Suter, H. R. MacDonald, and F. Radtke, “Jagged1-dependent Notch signaling is dispensable for hematopoietic stem cell self-renewal and differentiation,” Blood, vol. 105, no. 6, pp. 2340–2342, 2005.
[145]
Y. W. Kim, B. K. Koo, H. W. Jeong et al., “Defective Notch activation in microenvironment leads to myeloproliferative disease,” Blood, vol. 112, no. 12, pp. 4628–4638, 2008.
[146]
M. Santaguida, K. Schepers, B. King et al., “JunB protects against myeloid malignancies by limiting hematopoietic stem cell proliferation and differentiation without affecting self-renewal,” Cancer Cell, vol. 15, no. 4, pp. 341–352, 2009.
[147]
W. K. Clements, A. D. Kim, K. G. Ong, J. C. Moore, N. D. Lawson, and D. Traver, “A somitic Wnt16/Notch pathway specifies haematopoietic stem cells,” Nature, vol. 474, no. 7350, pp. 220–224, 2011.
[148]
R. B. Chalamalasetty, W. C. Dunty Jr., K. K. Biris et al., “The Wnt3a/β-catenin target gene Mesogenin1 controls the segmentation clock by activating a Notch signalling program,” Nature Communications, vol. 2, no. 1, article 390, 2011.
[149]
S. Han, N. Dziedzic, P. Gadue, G. M. Keller, and V. Gouon-Evans, “An endothelial cell niche induces hepatic specification through dual repression of Wnt and notch signaling,” Stem Cells, vol. 29, no. 2, pp. 217–228, 2011.
[150]
I. S. Peter and E. H. Davidson, “A gene regulatory network controlling the embryonic specification of endoderm,” Nature, vol. 474, no. 7353, pp. 635–639, 2011.
[151]
D. W. Kim, J. S. Lee, E. S. Yoon, B. I. Lee, S. H. Park, and E. S. Dhong, “Influence of human adipose-derived stromal cells on Wnt signaling in organotypic skin culture,” Journal of Craniofacial Surgery, vol. 22, no. 2, pp. 694–698, 2011.
[152]
N. Sato, L. Meijer, L. Skaltsounis, P. Greengard, and A. H. Brivanlou, “Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor,” Nature Medicine, vol. 10, no. 1, pp. 55–63, 2004.
[153]
P. S. Woll, J. K. Morris, M. S. Painschab et al., “Wnt signaling promotes hematoendothelial cell development from human embryonic stem cells,” Blood, vol. 111, no. 1, pp. 122–131, 2008.
[154]
C. H. Wu and R. Nusse, “Ligand receptor interactions in the Wnt signaling pathway in Drosophila,” Journal of Biological Chemistry, vol. 277, no. 44, pp. 41762–41769, 2002.
[155]
H. C. Wong, A. Bourdelas, A. Krauss et al., “Direct binding of the PDZ domain of Dishevelled to a conserved internal sequence in the C-terminal region of Frizzled,” Molecular Cell, vol. 12, no. 5, pp. 1251–1260, 2003.
[156]
N. S. Tolwinski, M. Wehrli, A. Rives, N. Erdeniz, S. DiNardo, and E. Wieschaus, “Wg/Wnt signal can be transmitted through arrow/LRP5,6 and axin independently of Zw3/Gsk3β activity,” Developmental Cell, vol. 4, no. 3, pp. 407–418, 2003.
[157]
T. Kramps, O. Peter, E. Brunner et al., “Wnt/Wingless signaling requires BCL9/legless-mediated recruitment of pygopus to the nuclear β-catenin-TCF complex,” Cell, vol. 109, no. 1, pp. 47–60, 2002.
[158]
M. Katoh and M. Katoh, “Identification and characterization of human BCL9L gene and mouse Bcl9l gene in silico,” International Journal of Molecular Medicine, vol. 12, no. 4, pp. 643–649, 2003.
[159]
J. R. Miller, A. M. Hocking, J. D. Brown, and R. T. Moon, “Mechanism and function of signal transduction by the Wnt/B-catenin and Wnt/Ca2+ pathways,” Oncogene, vol. 18, no. 55, pp. 7860–7872, 1999.
[160]
M. N. Chamorro, D. R. Schwartz, A. Vonica, A. H. Brivanlou, K. R. Cho, and H. E. Varmus, “FGF-20 and DKK1 are transcriptional targets of β-catenin and FGF-20 is implicated in cancer and development,” The EMBO Journal, vol. 24, no. 1, pp. 73–84, 2005.
[161]
D. Pennica, T. A. Swanson, J. W. Welsh et al., “WISP genes are members of the connective tissue growth factor family that are up-regulated in Wnt-1-transformed cells and aberrantly expressed in human colon tumors,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 25, pp. 14717–14722, 1998.
[162]
T. C. He, A. B. Sparks, C. Rago et al., “Identification of c-MYC as a target of the APC pathway,” Science, vol. 281, no. 5382, pp. 1509–1512, 1998.
[163]
O. Tetsu and F. McCormick, “β-catenin regulates expression of cyclin D1 in colon carcinoma cells,” Nature, vol. 398, no. 6726, pp. 422–426, 1999.
[164]
J. A. Kim, Y. J. Kang, G. Park et al., “Identification of a stroma-mediated Wnt/β-catenin signal promoting self-renewal of hematopoietic stem cells in the stem cell niche,” Stem Cells, vol. 27, no. 6, pp. 1318–1329, 2009.
[165]
T. C. Luis, F. Weerkamp, B. A. E. Naber et al., “Wnt3a deficiency irreversibly impairs hematopoietic stem cell self-renewal and leads to defects in progenitor cell differentiation,” Blood, vol. 113, no. 3, pp. 546–554, 2009.
[166]
M. Scheller, J. Huelsken, F. Rosenbauer et al., “Hematopoietic stem cell and multilineage defects generated by constitutive β-catenin activation,” Nature Immunology, vol. 7, no. 10, pp. 1037–1047, 2006.
[167]
P. Kirstetter, K. Anderson, B. T. Porse, S. E. W. Jacobsen, and C. Nerlov, “Activation of the canonical Wnt pathway leads to loss of hematopoietic stem cell repopulation and multilineage differentiation block,” Nature Immunology, vol. 7, no. 10, pp. 1048–1056, 2006.
[168]
J. J. Trowbridge, A. Xenocostas, R. T. Moon, and M. Bhatia, “Glycogen synthase kinase-3 is an in vivo regulator of hematopoietic stem cell repopulation,” Nature Medicine, vol. 12, no. 1, pp. 89–98, 2006.
[169]
H. E. Fleming, V. Janzen, C. Lo Celso et al., “Wnt signaling in the niche enforces hematopoietic stem cell quiescence and is necessary to preserve self-renewal in vivo,” Cell Stem Cell, vol. 2, no. 3, pp. 274–283, 2008.
[170]
K.-H. Ko, T. Holmes, P. Palladinetti et al., “GSK-3β inhibition promotes engraftment of ex vivo-expanded hematopoietic stem cells and modulates gene expression,” Stem Cells, vol. 29, no. 1, pp. 108–118, 2011.
[171]
M. Kinder, C. Wei, S. G. Shelat et al., “Hematopoietic stem cell function requires 12/15-lipoxygenase-dependent fatty acid metabolism,” Blood, vol. 115, no. 24, pp. 5012–5022, 2010.
