References

1. Raff, M.C. Social controls on cell survival and cell death. Nature 1992, 356, 397–400.
2. Boulais, P.E.; Frenette, P.S. Making sense of hematopoietic stem cell niches. Blood 2015, 125, 2629–2671.
3. Robb, L. Cytokine receptors and hematopoietic differentiation. Oncogene 2007, 26, 6715–6723.
4. Rongvaux, A.; Takizawa, H.; Strowig, T.; Willinger, T.; Eynon, E.E.; Flavell, R.A.; Manz, M.G. Human hemato-lymphoid system mice: Current use and future potential for medicine. Annu. Rev. Immunol. 2013, 31, 635–674.
5. Gbyli, R.; Song, Y.; Halene, S. Humanized mice as preclinical models for myeloid malignancies. Biochem. Pharmacol. 2020, 174, 113794.
6. Osawa, M.; Hanada, K.; Hamada, H.; Nakauchi, H. Long-term lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell. Science 1996, 273, 242–245.
7. Sanjuan-Pla, A.; Macauley, I.C.; Jensen, C.T.; Wall, P.S.; Luis, T.C.; Mead, A.; Moore, S.; Carellla, C.; Matsuoka, S.; Bouriez-Jones, T.; et al. Platelet-biased stem cells reside at the apex of the haematopoietic stem-cell hierarchy. Nature 2013, 502, 232–236.
8. Yamamoto, R.; Morita, Y.; Ooehara, J.; Hamanaka, S.; Onodera, M.; Rudolph, K.L.; Ema, H.; Nakauchi, H. Clonal analysis unveils self-renewing lineage-restricted progenitors generated directly from hematopoietic stem cells. Cell 2013, 154, 1112–1126.
9. Shin, J.Y.; Hu, W.; Naramura, M.; Park, C.Y. High c-Kit expression identifies hematopoietic stem cells with impaired self-renewal and megakaryocytic bias. J. Exp. Med. 2014, 211, 217–231.
10. Mooney, C.J.; Cunningham, A.; Tsapogas, P.; Toellner, K.-M.; Brown, G. Selective expression of Flt3 within the mouse hematopoietic stem cell compartment. Int. J. Mol. Sci. 2017, 18, 1037.
11. Schuettpelz, L.G.; Borderding, J.N.; Christopher, M.D.; Gopalan, P.K.; Romine, M.P.; Herman, A.C.; Woloszynek, J.R.; Greenbaum, A.M.; Link, D.C. G-CSF regulates hematopoietic stem cell activity, in part, through activation of toll-like receptor signaling. Leukaemia 2014, 28, 1851–1860.
12. Kondo, M.; Scherer, D.C.; Miyamoto, T.; King, A.G.; Akashi, K.; Sugamura, K.; Weismann, I.L. Cell-fate conversion of lymphoid-committed progenitors by instructive cytokines. Nature 2000, 407, 383–386.
13. Gekas, C.; Graf, T. CD41 expression marks myeloid-biased adult hematopoietic stem cells and increases with age. Blood 2013, 121, 4463–4472.
14. Shimazu, T.; Iida, R.; Zhang, Q.; Weiner, R.S.; Medina, K.L.; Alberola-Ila, J.; Kincade, P.W. CD86 is expressed on murine hematopoietic stem cells and denotes lymphopoietic potential. Blood 2012, 119, 4889–4897.
15. Beerman, I.; Bhattacharaya, D.; Zandi, S.; Sigvardsson, M.; Weissman, I.L.; Bryder, D.; Rossi, D.J. Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion. Proc. Natl. Acad. Sci. USA 2010, 107, 5465–5470.
16. Notta, F.; Zandi, S.; Takayama, N.; Dobson, S.; Gan, O.I.; Wilson, G.; Kaufmann, K.B.; McLeod, J.; Laurenti, E.; Dunant, C.F.; et al. Distinct routes of lineage development reshape the human blood hierarchy across ontogeny. Science 2016, 351, aab2116.
17. Notta, F.; Doulatove, S.; Laurenti, E.; Poeppl, A.; Jurisica, I.; Dick, J.E. Isolation of single human hematopoietic stem cells capable of long-term multilineage engraftment. Science 2011, 333, 218–221.
18. Robin, C.; Bollerot, K.; Mendes, S.; Hoak, E.; Crisan, M.; Cerisoli, F.; Lauw, I.; Kaimakis, P.; Jorna, R.; Vermeulen, M.; et al. Human placenta is a potent hematopoietic niche containing hematopoietic stem and progenitor cells throughout development. Cell Stem Cell. 2009, 5, 385–395.
19. Yamazaki, S.; Ema, H.; Karlsson, G.; Yamaguchi, T.; Miyoshi, H.; Shioda, S.; Taketo, M.M.; Karlson, S.; Iwama, A.; Nakauchi, H. Nonmyelinating Schwann cells maintain hematopoietic stem cell hibernation in the bone marrow niche. Cell 2011, 147, 1146–1158.
20. Suda, T.; Takubo, K.; Semenza, G.L. Metabolic regulation of hematopoietic stem cells in the hypoxic niche. Cell Stem Cell 2011, 9, 298–310.
21. Calvi, L.M.; Adams, G.B.; Weibrecht, K.W.; Weber, J.M.; Olsen, D.P.; Knight, M.C.; Martin, R.P.; Shipani, M.E.; Divieti, P.; Bringhurst, F.R.; et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 2003, 425, 841–846.
22. Mancini, S.J.C.; Montei, N.M.; Dumortier, A.; Sutur, U.; MacDonald, H.R.; Radtke, F. Jagged-dependent Notch signalling is dispensible for hematopoietic stem cell self-renewal and differentiation. Blood 2005, 105, 2340–2342.
23. Zhang, J.; Niu, C.; Ye, L.; Huang, H.; He, X.; Tong, W.-G.; Ross, J.; Haug, J.; Johnson, T.; Feng, J.Q.; et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature 2003, 425, 836–841.
24. Bromberg, O.; Frisch, B.J.; Weber, J.M.; Porter, R.L.; Civitelli, R.; Calvi, L.M. Osteoblastic N-cadherin is not required for microenvironmental support and regulation of hematopoietic stem and progenitor cells. Blood 2012, 120, 303–313.
25. Stier, S.; Ko, Y.; Forkert, R. Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size. J. Exp. Med. 2005, 201, 1781–1791.
26. Kollet, O.; Dar, A.; Shivtiel, S.; Kalinkovich, A.; Lapid, K.; Sztainberg, Y.; Tesio, M.; Samstein, R.M.; Goichberg, P.; Spiegel, A.; et al. Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells. Nat. Med. 2006, 12, 657–664.
27. Shook, B.; Gonzablez, S.E.; Grisotti, G.; Zwick, R.; Horsley, V. The role of adipocytes in tissue regeneration and stem cell niches. Ann. Rev. Cell Dev. Biol. 2016, 32, 609–631.
28. Spangrude, G.J.; Heimfeld, S.; Weissman, I.L. Purification and characterization of mouse hematopoietic stem cells. Science 1988, 241, 58–62.
29. Ceredig, R.; Rolink, A.G.; Brown, G. Models of haematopoiesis: Seeing the wood for the trees. Nat. Rev. Immunol. 2009, 9, 293–300.
30. Nestorowa, S.; Hamey, F.K.; Pijuane Sala, B.; Diamanti, E.; Sheperd, M.; Laurenti, E.; Wilson, N.K.; Kent, D.G.; Gottens, B. A single cell resolution map of mouse hematopoietic stem and progenitor cell differentiation. Blood 2016, 128, e20–e31.
31. Psaila, B.; Mead, A.J. Sinlge cell aproaches reveal novel pathways for megakaryocyte and erythroid differnetiation. Blood 2019, 133, 1427–1435.
32. Balciunaite, E.; Ceredig, R.; Rolink, A.G. The earliest subpopulations of mouse thymocytes contains potent T, significant macrophage and natural killer cell but no B-lymphocyte potential. Blood 2005, 105, 1930–1936.
33. Glatman Zaretsky, A.; Taylor, J.J.; King, I.L.; Marshall, F.A.; Mohrs, M.; Pearce, E.J. T follicular helper cells differentiate from th2 cells in response to helminth antigens. J. Exp. Med. 2009, 206, 991–999.
34. Singh, K.; Gatzka, M.; Peters, T.; Borkner, L.; Hainzl, A.; Wang, H.; Sindrilaru, A.; Scharffetter-Kochanek, K. Reduced cd18 levels drive regulatory t cell conversion into th17 cells in the cd18hypo pl/j mouse model of psoriasis. J. Immunol. 2013, 190, 2544–2553.
35. Kim, B.S.; Kim, I.K.; Park, Y.J.; Kim, Y.S.; Kim, Y.J.; Chang, W.S.; Lee, Y.S.; Kweon, M.N.; Chung, Y.; Kang, C.Y. Conversion of th2 memory cells into foxp3+ regulatory T cells suppressing th2-mediated allergic asthma. Proc. Natl. Acad. Sci. USA 2010, 107, 8742–8747.
36. Eizenberg-Magar, I.; Rimer, J.; Zaretsky, I.; Lara-Astiaso, D.; Reich-Zeliger, S.; Friedman, N. Diverse continuum of cd4(+) t-cell states is determined by hierarchical additive integration of cytokine signals. Proc. Natl. Acad. Sci. USA 2017, 114, E6447–E6456.
37. Chang, H.H.; Hemberg, M.; Barahana, M.; Ingber, D.E.; Huang, S. Transcriptome-wide noise controls lineage choice in mammalian progenitor cells. Nature 2008, 453, 544–547.
38. Teles, J.; Pina, C.; Eden, P.; Ohlsson, M.; Enver, T.; Peterson, C. Transcriptional regulation of lineage commitment—A stochastic model of cell fate decisions. PLoS Comput. Biol. 2013, 98, e1003197.
39. Seshasayee, D.; Gaines, P.; Wojehowski, D.M. GATA-1 dominantly activates a program of erythroid gene expression in factor-dependent myeloid FDCW2 cells. Mol. Cell. Biol. 1998, 18, 3278–3288.
40. Gaine, M.E.; Sharpe, D.J.; Smith, J.S.; Colyer, H.A.A.; Hodges, V.M.; Lappin, T.R.; Mills, K.I. GATA2 regulates the erythropoietin receptor in t(12;21) ALL. Oncotarget 2017, 8, 66061–66074.
41. Vicente, C.; Conchillo, A.; Garcia-Sanchez, M.A.; Odero, M.D. The role of the GATA2 transcription factor in normal and malignant hematopoiesis. Crit. Rev. Oncol. Hematol. 2012, 82, 1–17.
42. Barroso, G.V.; Puzovic, N.; Dutheil, J.Y. The evolution of gene-specific transcriptional noise is driven by selection at the pathway level. Genetics 2018, 208, 1173–1189.
43. Doi, Y.; Yokota, Y.; Satoh, Y.; Okuzaki, D.; Tokunaga, M.; Ishibashi, T.; Sudo, T.; Ueda, T.; Shingai, Y.; Ichi, M. Variable SATB1 levels regulate hematopoietic stem cell heterogeneity with distinct lineage fates. Cell Rep. 2018, 23, 3223–3235.
44. Lund, R.J.; Narva, E.; Lahesmaa, R. Genetic and epigenetic stability of human pluripotent stem cells. Nat. Rev. Genet. 2012, 13, 732–744.
45. Hu, M.; Krause, D.; Greaves, M.; Sharkis, S.; Dexter, M.; Heyworth, C.; Enver, T. Multilineage gene expression precedes commitment in the hematopoietic system. Genes Dev. 1997, 11, 774–785.
46. Mossadegh-Keller, N.; Sarrazin, S.; Kandalla, P.K.; Espinosa, L.; Stanley, E.R.; Nutt, S.L.; Moore, J.; Sieweke, M.H. M-CSF instructs myeloid lineage fate in single haematopoietic stem cells. Nature 2013, 497, 239–243.
47. Metcalf, D.; Burgess, A.W. Clonal analysis of progenitor cell commitment of granulocyte or macrophage production. J. Cell. Physiol. 1982, 111, 275–283.
48. Rieger, M.A.; Hoppe, P.S.; Smejkal, B.M.; Eitelhuber, A.C.; Schroeder, T. Hematopoietic cytokines can instruct lineage choice. Science 2009, 325, 217–218.
49. Grover, A.; Mancini, E.; Moore, S.; Mead, A.J.; Atkinson, D.; Rasmussen, K.D.; O’Carroll, D.; Jacobsen, S.E.; Nerlove, C. Erythropoietin guides multipotent hematopoietic progenitor cells towards an erythroid fate. J. Exp. Med. 2014, 211, 181–188.
50. Tsapogas, P.; Swee, L.K.; Nusser, A.; Nuber, N.; Kreuzaler, M.; Capoferri, G.; Rolink, H.; Ceredig, R.; Rolink, A. In vivo evidence for an instructive role of fms-like tyrosine kinase-3 (FLT3) ligand in hematopoietic development. Haematologica 2014, 99, 638–646.
51. Luis, T.; Barkas, N.; Giustacchini, A.; Guerrero, J.; Wu, B.; Bouriez-Jones, T.; Macaulay, I.; Mead, A.; Nerlove, C.; Ghevaert, C.; et al. Perivascular niche cells sense thrombocytopenia and activate platelet-biased HSCs in an IL-1 dependent manner. Exp. Hematol. 2019, 76, S77.
52. Singh, R.P.; Grinenko, T.; Ramasz, B.; Franke, K.; Lesche, M.; Dahl, A.; Gassman, M.; Chavakis, T.; Henry, I.; Wielockx, B. Hematopoietic stem cells but not multipotent progenitors drive erythropoiesis during chronic erythroid stress in Epo transgenic mice. Stem Cell Rep. 2018, 10, 1908–1919.
53. Colmore, A.; Amorim, M.; Pontier, A.L.; Wang, S.; Jablonski, E.; Sipkins, D.A. Leukaemia cells create bone marrow niches that disrupt the behaviour of normal hematopoietic progenitor cells. Science 2008, 322, 1861–1865.
54. Zwezdaryk, K.J.; Coffelt, S.B.; Figueroa, Y.G.; Liu, J.; Phinney, D.G.; LaMarca, H.L.; Florez, L.; Morris, C.B.; Hoyle, G.W.; Scandurro, A.B. Erythropoietin, a hypoxia-regulated factor, elicits a pro-angiogenic program in human mesenchymal stem cells. Exp. Hematol. 2007, 35, 640–652.
55. Anagnostou, A.; Lee, E.S.; Keissiman, N.; Levinson, R.; Steiner, M. Erytrhopoietin has a mitogenic and postive chemotactic effect on endothelial cells. Proc. Natl. Acad. Sci. USA 1990, 87, 5082–5972.
56. Poniewierska-Baran, A.; Rajewska, J.R.; Ratajczak, M.Z. Erythropoietin enhances migration of human nuroblastoma cells: In vitro studies and potential therapeutic implication. J. Cancer Stem Cell Res. 2017, 5, e1003.
57. Fuller, K.; Owens, J.M.; Jagger, A.; Wilson, A.; Moss, R.; Chambers, T.J. Macrophage colony-stimulating factors stimulates survival and chemotactic behaviour in isolated osteoclasts. J. Exp. Med. 1993, 178, 1733–1744.
58. Wang, J.M.; Griffin, J.D.; Rambaldi, A.; Chen, Z.D.; Mantovani, A. Induction of monocyte migration by recombinant macrophage colony-stimulating factor. J. Immunol. 1988, 141, 575–579.
59. Vedham, V.; Phee, H.; Coggeshall, K.M. Vav activation and function as a Rac guanine nucleotide exchange factor in macrophage colony-stimulating factor-induced macrophage chemotaxis. Mol. Cell. Biol. 2005, 25, 4211–4220.
60. Pierce, J.H.; Di Marco, E.; Cox, G.W.; Lombardi, D.; Ruggiero, M.; Varesio, L.; Wang, L.M.; Choudhury, G.C.; Sakaguchi, A.Y.; Di Fiore, P.P. Macrophage-colony-stimulating factor (CSF-1) induces proliferation, chemotaxis, and reversible monocytic differentiation in myeloid progenitor cells transfected with human c-fms/CSF-1 receptor cDNA. Proc. Natl. Acad. Sci. USA 1990, 87, 5613–5617.
61. Gomez-Cambronero, J.; Horn, J.; Paul, C.C.; Baumann, M.A. Granulocyte-macrophage colony-stimulating factor is a chemoattractant cytokine for human neutrophils: Involvement of the ribosomal p70 S6 kinase signalling pathway. J. Immunol. 2003, 171, 6846–6855.
62. Bussolino, F.; Wang, J.M.; Defilippi, P.; Turrini, F.; Sanavio, F.; Edgell, J.; Aglietta, M.; Arese, P.; Mantovani, A. Granulocyte- and granulocyte-macrophage-colony stimulating factors induce human endothelial cells to migrate and proliferate. Nature 1989, 337, 471–473.
63. Vaillant, P.; Muller, V.; Martinet, Y.; Martinet, N. Human granulocyte and granulocyte-macrophage-colony stimulating factors are chemotactic and “competence” growth factors for human mesenchymal cells. Biochem. Biophys. Res. Commun. 1993, 192, 879–885.
64. Brown, G.; Ceredig, R. Modelling the hematopoietic landscape. Front. Cell. Dev. Biol. 2019, 7, 104.
65. Sugima, R.; Jha, D.K.; Han, A.; Soria-Vallas, C.; da Rocha, E.L.; Lu, Y.-F.; Goettel, J.A.; Serro, E.; Rowe, R.G.; Malleshaiah, M.; et al. Haematopoetic stem and progenitor cells from human pluripotent cells. Nature 2017, 545, 432–438.
66. Torisawa, Y.-S.; Spina, C.S.; Mammoto, T.; Mammoto, A.; Weaver, J.C.; Tat, T.; Collins, J.J.; Ingbar, D.E. Bone marrow-on-a-chip replicates hematopoietic niche physiology in vitro. Nat. Methods 2014, 11, 663–669.
67. Bourgine, P.E.; Klein, T.; Paczulla, A.M.; Shimizu, T.; Kunz, L.; Kokkaliaris, K.D.; Coutu, D.L.; Lengerke, C.; Skoda, R.; Schroeder, T.; et al. In vitro biomimetic engineering of a human hematopoietic niche with functional properties. Proc. Natl. Acad. Sci. USA 2018, 115, E5688–E5695.
68. Bonnet, D.; Dick, J.E. Human acute myeloid leukaemia is organised as a hierarchy that originates from a primitive haematopoietic cell. Nat. Med. 1997, 197, 461–463.
69. Vicente-Duenas, C.; Perez-Caro, M.; Abollo-Jimenez, F.; Cobaleda, C.; Sanchez-Garcia, I. Stem-cell driven cancer: “hands-off” regulation of cancer development. Cell Cycle 2009, 8, 1314–1318.
70. Agiaz-Doblas, A.; Bueno, C.; Bashford-Rogers, R.; Roy, A.; Schnieder, P.; Bardini, M.; Ballerini, P.; Cazzaniga, G.; Moreno, T.; Revilla, C.; et al. Unravelling the cellular origin and clinical prognostic markers of infant B-cell acute lymphoblastic luekemia using genome-wide analysis. Haematologica 2019, 104, 1176–1188.
71. Cox, C.V.; Blair, A. A primitive cell origin for B-cell precursor ALL? Stem Cell Rev. 2005, 1, 189–196.
72. Edwards, R.H.; Wasik, M.A.; Finan, J.; Rodriguez, R.; Moore, J.; Kamoun, M.; Rennert, H.; Bird, J.; Nowell, P.C.; Salhang, K.E. Evidence for early hematopoietic progenitor cell involvement in acute promyelocytic leukemia. Am. J. Clin. Pathol. 1999, 112, 819–827.
73. Garcia-Ramirez, I.; Bhatia, S.; Rodriguez-Hernandez, G.; Gonzalez-Herrero, I.; Walter, C.; Gonzalez de Tena-Davila, S.; Parvin, S.; Haas, O.; Woessmann, W.; Stanulla, M.; et al. Lmo2 expression defines tumor cell identity during T-cell leukemogenesis. EMBO J. 2018, 37, e98783.
74. Martin-Lorenzo, A.; Auer, F.; Chan, L.N.; Garcia-Ramirez, I.; Gonzalez-Herrero, I.; Rodriguez-Hernandez, G.; Bartenhagen, C.; Dugas, M.; Gombert, M.; Ginzel, S.; et al. Loss of Pax5 Exploits Sca1-BCR-ABL(p190) susceptibility to confer the metabolic shift essential for pB-ALL. Cancer Res. 2018, 78, 2669–2679.
75. Perez-Caro, M.; Cobaleda, C.; Gonzalez-Herrero, I.; Vicente-Duenas, C.; Bermejo-Rodriguez, C.; Sanchez-Beato, M.; Orfao, A.; Pintado, B.; Flores, T.; Sanchez-Martin, M.; et al. Cancer induction by restriction of oncogene expression to the stem cell compartment. EMBO J. 2009, 28, 8–20.
76. Brown, G.; Sanchez-Garcia, I. Is lineage decision-making restricted during tumoral reprograming of haematopoietic stem cells? Oncotarget 2015, 6, 43326–43341.
77. Nishi, K.; Katayama, N.; Miwa, H.; Shikami, M.; Masuya, M.; Shiki, H.; Kila, K. The survival of human leukemic B-cell precursors is supported by stromal cells and cytokines associated with the expression of bcl-2 protein. Br. J. Haematol. 1995, 105, 701–710.
78. Hiwase, D.K.; White, D.L.; Powell, J.A.; Saunders, V.A.; Zrim, S.A.; Frede, A.K.; Guthridge, M.A.; Lopez, A.F.; D’Andrea, R.J.; To, L.B.; et al. Blocking cytokine signalling along with intense bcr-Abl kinase inhibition induces apopotosis in primary CML progenitors. Leukemia 2010, 24, 771–778.