Development of Hematopoietic Stem Cells in Zebrafish

  • Isao KobayashiEmail author


Hematopoietic stem cells (HSCs) are a rare population of cells with the remarkable abilities to both self-renew and differentiate into all types of mature blood cells. Understanding of the developmental mechanisms of HSCs is of great importance to instruct and expand HSCs from pluripotent precursors, such as induced pluripotent stem cells (iPSCs). The zebrafish is a unique vertebrate model in which numerous elegant experimental approaches can be applied to the study of HSC development, including live-imaging, chemical and genetic screening, and genome editing. HSCs are specified from a shared vascular precursor, the angioblast, and arise directly from the ventral floor of the dorsal aorta. HSCs then migrate to a transient hematopoietic organ, the caudal hematopoietic tissue, where microenvironmental niche cells promote the expansion of HSCs prior to the colonization of the kidney, the final adult hematopoietic organ in zebrafish. Over the past decade, a number of intrinsic and extrinsic signaling molecules involved in the specification, maintenance, migration, and proliferation of HSCs have been identified in the zebrafish embryo. Importantly, despite evolutional divergence, the genetic programs governing HSC development are highly conserved among vertebrates, indicating that studies in zebrafish may be translated to regenerative medicine using human iPSCs. This chapter highlights the current knowledge and recent advances regarding the cellular origin and molecular regulation of HSC development in zebrafish.


Hematopoietic stem cell Hemogenic endothelium Angioblast Dorsal aorta Caudal hematopoietic tissue Definitive hematopoiesis 


  1. Beerman I, Luis TC, Singbrant S, Lo Celso C, Méndez-Ferrer S (2017) The evolving view of the hematopoietic stem cell niche. Exp Hematol 50:22e6CrossRefGoogle Scholar
  2. Bertrand JY, Giroux S, Golub R et al (2005) Characterization of purified intraembryonic hematopoietic stem cells as a tool to define their site of origin. Proc Natl Acad Sci U S A 102:134–139CrossRefPubMedGoogle Scholar
  3. Bertrand JY, Kim AD, Violette EP, Stachura DL, Cisson JL, Traver D (2007) Definitive hematopoiesis initiates through a committed erythromyeloid progenitor in the zebrafish embryo. Development 134:4147–4156CrossRefPubMedPubMedCentralGoogle Scholar
  4. Bertrand JY, Chi NC, Santoso B, Teng S, Stainier DY, Traver D (2010) Haematopoietic stem cells derive directly from aortic endothelium during development. Nature 464:108–111CrossRefPubMedPubMedCentralGoogle Scholar
  5. Blaser BW, Moore JL, Hagedorn EJ et al (2017) CXCR1 remodels the vascular niche to promote hematopoietic stem and progenitor cell engraftment. J Exp Med 214:1011–1027CrossRefPubMedPubMedCentralGoogle Scholar
  6. Boisset JC, van Cappellen W, Andrieu-Soler C, Galjart N, Dzierzak E, Robin C (2010) In vivo imaging of haematopoietic cells emerging from the mouse aortic endothelium. Nature 464:116–120CrossRefPubMedGoogle Scholar
  7. Bozkulak EC, Weinmaster G (2009) Selective use of ADAM10 and ADAM17 in activation of Notch1 signaling. Mol Cell Biol 29:5679–5695CrossRefPubMedPubMedCentralGoogle Scholar
  8. Bradbury J (2004) Small fish, big science. PLoS Biol 2:E148CrossRefPubMedPubMedCentralGoogle Scholar
  9. Brou C, Logeat F, Gupta N et al (2000) A novel proteolytic cleavage involved in notch signaling: the role of the disintegrin-metalloprotease TACE. Mol Cell 5:207–216CrossRefPubMedGoogle Scholar
  10. Brown LA, Rodaway AR, Schilling TF et al (2000) Insights into early vasculogenesis revealed by expression of the ETS-domain transcription factor Fli-1 in wild-type and mutant zebrafish embryos. Mech Dev 90:237–252CrossRefPubMedGoogle Scholar
  11. Burns CE, DeBlasio T, Zhou Y, Zhang J, Zon L, Nimer SD (2002) Isolation and characterization of runxa and runxb, zebrafish members of the runt family of transcriptional regulators. Exp Hematol 30:1381–1389CrossRefPubMedGoogle Scholar
  12. Burns CE, Traver D, Mayhall E, Shepard JL, Zon LI (2005) Hematopoietic stem cell fate is established by the notch-Runx pathway. Genes Dev 19:2331–2342CrossRefPubMedPubMedCentralGoogle Scholar
  13. Butko E, Distel M, Pouget C et al (2015) Gata2b is a restricted early regulator of hemogenic endothelium in the zebrafish embryo. Development 142:1050–1061CrossRefPubMedPubMedCentralGoogle Scholar
  14. Byrd N, Becker S, Maye P et al (2002) Hedgehog is required for murine yolk sac angiogenesis. Development 129:361–372PubMedGoogle Scholar
  15. Chen W, Casey Corliss D (2004) Three modules of zebrafish mind bomb work cooperatively to promote Delta ubiquitination and endocytosis. Dev Biol 267:361–373CrossRefPubMedGoogle Scholar
  16. Chen MJ, Yokomizo T, Zeigler BM, Dzierzak E, Speck NA (2009) Runx1 is required for the endothelial to haematopoietic cell transition but not thereafter. Nature 457:887–891CrossRefPubMedPubMedCentralGoogle Scholar
  17. Cheshier SH, Morrison SJ, Liao X, Weissman IL (1999) In vivo proliferation and cell cycle kinetics of long-term self-renewing hematopoietic stem cells. Proc Natl Acad Sci U S A 96:3120–3125CrossRefPubMedPubMedCentralGoogle Scholar
  18. Chin AJ, Chen JN, Weinberg ES (1997) Bone morphogenetic protein-4 expression characterizes inductive boundaries in organs of developing zebrafish. Dev Genes Evol 207:107–114CrossRefPubMedGoogle Scholar
  19. Clements WK, Traver D (2013) Signalling pathways that control vertebrate haematopoietic stem cell specification. Nat Rev Immunol 13:336–348CrossRefPubMedPubMedCentralGoogle Scholar
  20. Clements WK, Kim AD, Ong KG, Moore JC, Lawson ND, Traver D (2011) A somitic Wnt16/notch pathway specifies haematopoietic stem cells. Nature 474:220–224CrossRefPubMedPubMedCentralGoogle Scholar
  21. Cortes M, Chen MJ, Stachura DL et al (2016) Developmental vitamin D availability impacts hematopoietic stem cell production. Cell Rep 17:458–468CrossRefPubMedPubMedCentralGoogle Scholar
  22. Cumano A, Dieterlen-Lievre F, Godin I (1996) Lymphoid potential, probed before circulation in mouse, is restricted to caudal intraembryonic splanchnopleura. Cell 86:907–916CrossRefPubMedGoogle Scholar
  23. Davidson AJ, Zon LI (2004) The ‘definitive’ (and ‘primitive’) guide to zebrafish hematopoiesis. Oncogene 23:7233–7246CrossRefPubMedGoogle Scholar
  24. Davis GE, Senger DR (2005) Endothelial extracellular matrix: biosynthesis, remodeling, and functions during vascular morphogenesis and neovessel stabilization. Circ Res 97:1093–1107CrossRefPubMedGoogle Scholar
  25. de Bruijn MF, Speck NA, Peeters MC, Dzierzak E (2000) Definitive hematopoietic stem cells first develop within the major arterial regions of the mouse embryo. EMBO J 19:2465–2474CrossRefPubMedPubMedCentralGoogle Scholar
  26. de Bruijn MF, Ma X, Robin C, Ottersbach K, Sanchez MJ, Dzierzak E (2002) Hematopoietic stem cells localize to the endothelial cell layer in the midgestation mouse aorta. Immunity 16:673–683CrossRefPubMedGoogle Scholar
  27. de Jong JL, Zon LI (2005) Use of the zebrafish system to study primitive and definitive hematopoiesis. Annu Rev Genet 39:481–501CrossRefPubMedGoogle Scholar
  28. de Pater E, Kaimakis P, Vink CS et al (2013) Gata2 is required for HSC generation and survival. J Exp Med 210:2843–2850CrossRefPubMedPubMedCentralGoogle Scholar
  29. Detrich HW, Kieran MW, Chan FY et al (1995) Intraembryonic hematopoietic cell migration during vertebrate development. Proc Natl Acad Sci U S A 92:10713–10717CrossRefPubMedPubMedCentralGoogle Scholar
  30. Ding L, Saunders TL, Enikolopov G, Morrison SJ (2012) Endothelial and perivascular cells maintain haematopoietic stem cells. Nature 481:457–462CrossRefPubMedPubMedCentralGoogle Scholar
  31. Dooley KA, Davidson AJ, Zon LI (2005) Zebrafish scl functions independently in hematopoietic and endothelial development. Dev Biol 277:522–536CrossRefPubMedGoogle Scholar
  32. Dyer MA, Farrington SM, Mohn D, Munday JR, Baron MH (2001) Indian hedgehog activates hematopoiesis and vasculogenesis and can respecify prospective neurectodermal cell fate in the mouse embryo. Development 128:1717–1730PubMedGoogle Scholar
  33. Dzierzak E, Medvinsky A (1995) Mouse embryonic hematopoiesis. Trends Genet 11:359–366CrossRefPubMedGoogle Scholar
  34. Ehninger A, Trumpp A (2011) The bone marrow stem cell niche grows up: mesenchymal stem cells and macrophages move in. J Exp Med 208:421–428CrossRefPubMedPubMedCentralGoogle Scholar
  35. Ema H, Nakauchi H (2000) Expansion of hematopoietic stem cells in the developing liver of a mouse embryo. Blood 95:2284–2288PubMedGoogle Scholar
  36. Espín-Palazón R, Stachura DL, Campbell CA et al (2014) Proinflammatory signaling regulates hematopoietic stem cell emergence. Cell 159:1070–1085CrossRefPubMedPubMedCentralGoogle Scholar
  37. Fraser ST, Ogawa M, Yu RT, Nishikawa S, Yoder MC (2002) Definitive hematopoietic commitment within the embryonic vascular endothelial-cadherin(+) population. Exp Hematol 30:1070–1078CrossRefPubMedGoogle Scholar
  38. Gagnon JA, Valen E, Thyme SB et al (2014) Efficient mutagenesis by Cas9 protein-mediated oligonucleotide insertion and large-scale assessment of single-guide RNAs. PLoS One 9:e98186CrossRefPubMedPubMedCentralGoogle Scholar
  39. Galloway JL, Zon LI (2003) Ontogeny of hematopoiesis: examining the emergence of hematopoietic cells in the vertebrate embryo. Curr Top Dev Biol 53:139–158CrossRefPubMedGoogle Scholar
  40. Gao X, Johnson KD, Chang YI et al (2013) Gata2 cis-element is required for hematopoietic stem cell generation in the mammalian embryo. J Exp Med 210:2833–2842CrossRefPubMedPubMedCentralGoogle Scholar
  41. Gekas C, Dieterlen-Lièvre F, Orkin SH, Mikkola HK (2005) The placenta is a niche for hematopoietic stem cells. Dev Cell 8:365–375CrossRefPubMedGoogle Scholar
  42. Genthe JR, Clements WK (2017) R-spondin 1 is required for specification of hematopoietic stem cells through Wnt16 and Vegfa signaling pathways. Development 144:590–600CrossRefPubMedPubMedCentralGoogle Scholar
  43. Gering M, Patient R (2005) Hedgehog signaling is required for adult blood stem cell formation in zebrafish embryos. Dev Cell 8:389–400CrossRefPubMedGoogle Scholar
  44. Godin I, Cumano A (2002) The hare and the tortoise: an embryonic haematopoietic race. Nat Rev Immunol 2:593–604CrossRefPubMedGoogle Scholar
  45. Goessling W, North TE, Loewer S et al (2009) Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration. Cell 136:1136–1147CrossRefPubMedPubMedCentralGoogle Scholar
  46. Grainger S, Richter J, Palazón RE et al (2016) Wnt9a is required for the aortic amplification of nascent hematopoietic stem cells. Cell Rep 17:1595–1606CrossRefPubMedGoogle Scholar
  47. Hadland BK, Huppert SS, Kanungo J et al (2004) A requirement for Notch1 distinguishes 2 phases of definitive hematopoiesis during development. Blood 104:3097–3105CrossRefPubMedPubMedCentralGoogle Scholar
  48. He Q, Zhang C, Wang L et al (2015) Inflammatory signaling regulates hematopoietic stem and progenitor cell emergence in vertebrates. Blood 125:1098–1106CrossRefPubMedGoogle Scholar
  49. Heissig B, Hattori K, Friedrich M, Rafii S, Werb Z (2003) Angiogenesis: vascular remodeling of the extracellular matrix involves metalloproteinases. Curr Opin Hematol 10:136–141CrossRefPubMedGoogle Scholar
  50. Henninger J, Santoso B, Hans S et al (2017) Clonal fate mapping quantifies the number of haematopoietic stem cells that arise during development. Nat Cell Biol 19:17–27CrossRefPubMedGoogle Scholar
  51. Hisano Y, Sakuma T, Nakade S et al (2015) Precise in-frame integration of exogenous DNA mediated by CRISPR/Cas9 system in zebrafish. Sci Rep 5:8841CrossRefPubMedPubMedCentralGoogle Scholar
  52. Hoggatt J, Kfoury Y, Scadden DT (2016) Hematopoietic stem cell niche in health and disease. Annu Rev Pathol 11:555–581CrossRefPubMedGoogle Scholar
  53. Hsia N, Zon LI (2005) Transcriptional regulation of hematopoietic stem cell development in zebrafish. Exp Hematol 33:1007–1014CrossRefPubMedGoogle Scholar
  54. Itoh M, Kim CH, Palardy G et al (2003) Mind bomb is a ubiquitin ligase that is essential for efficient activation of notch signaling by Delta. Dev Cell 4:67–82CrossRefPubMedGoogle Scholar
  55. Jao LE, Wente SR, Chen W (2013) Efficient multiplex biallelic zebrafish genome editing using a CRISPR nuclease system. Proc Natl Acad Sci U S A 110:13904–13909CrossRefPubMedPubMedCentralGoogle Scholar
  56. Jin SW, Beis D, Mitchell T, Chen JN, Stainier DY (2005) Cellular and molecular analyses of vascular tube and lumen formation in zebrafish. Development 132:5199–5209CrossRefPubMedGoogle Scholar
  57. Jin H, Xu J, Wen Z (2007) Migratory path of definitive hematopoietic stem/progenitor cells during zebrafish development. Blood 109:5208–5214CrossRefPubMedGoogle Scholar
  58. Jing L, Tamplin OJ, Chen MJ et al (2015) Adenosine signaling promotes hematopoietic stem and progenitor cell emergence. J Exp Med 212:649–663CrossRefPubMedPubMedCentralGoogle Scholar
  59. Johnson KD, Hsu AP, Ryu MJ et al (2012) Cis-element mutated in GATA2-dependent immunodeficiency governs hematopoiesis and vascular integrity. J Clin Invest 122:3692–3704CrossRefPubMedPubMedCentralGoogle Scholar
  60. Kalev-Zylinska ML, Horsfield JA, Flores MV et al (2002) Runx1 is required for zebrafish blood and vessel development and expression of a human RUNX1-CBF2T1 transgene advances a model for studies of leukemogenesis. Development 129:2015–2030PubMedGoogle Scholar
  61. Kawahara A, Hisano Y, Ota S, Taimatsu K (2016) Site-specific integration of exogenous genes using genome editing technologies in zebrafish. Int J Mol Sci 17:727CrossRefPubMedCentralGoogle Scholar
  62. Khan JA, Mendelson A, Kunisaki Y et al (2016) Fetal liver hematopoietic stem cell niches associate with portal vessels. Science 351:176–180CrossRefPubMedGoogle Scholar
  63. Kim AD, Melick CH, Clements WK et al (2014) Discrete notch signaling requirements in the specification of hematopoietic stem cells. EMBO J 33:2363–2373CrossRefPubMedPubMedCentralGoogle Scholar
  64. Kissa K, Herbomel P (2010) Blood stem cells emerge from aortic endothelium by a novel type of cell transition. Nature 464:112–115CrossRefPubMedGoogle Scholar
  65. Kobayashi I, Kobayashi-Sun J, Kim AD et al (2014) Jam1a-Jam2a interactions regulate haematopoietic stem cell fate through notch signalling. Nature 512:319–323CrossRefPubMedPubMedCentralGoogle Scholar
  66. Konantz M, Alghisi E, Müller JS et al (2016) Evi1 regulates notch activation to induce zebrafish hematopoietic stem cell emergence. EMBO J 35:2315–2331CrossRefPubMedPubMedCentralGoogle Scholar
  67. Kopan R, Ilagan MX (2009) The canonical notch signaling pathway: unfolding the activation mechanism. Cell 137:216–233CrossRefPubMedPubMedCentralGoogle Scholar
  68. Krebs LT, Xue Y, Norton CR et al (2000) Notch signaling is essential for vascular morphogenesis in mice. Genes Dev 14:1343–1352PubMedPubMedCentralGoogle Scholar
  69. Kwan W, Cortes M, Frost I et al (2016) The central nervous system regulates embryonic HSPC production via stress-responsive glucocorticoid receptor signaling. Cell Stem Cell 19:370–382CrossRefPubMedPubMedCentralGoogle Scholar
  70. Lapidot T, Dar A, Kollet O (2005) How do stem cells find their way home? Blood 106:1901–1910CrossRefPubMedGoogle Scholar
  71. Lawson ND, Weinstein BM (2002) In vivo imaging of embryonic vascular development using transgenic zebrafish. Dev Biol 248:307–318CrossRefPubMedGoogle Scholar
  72. Lawson ND, Vogel AM, Weinstein BM (2002) Sonic hedgehog and vascular endothelial growth factor act upstream of the notch pathway during arterial endothelial differentiation. Dev Cell 3:127–136CrossRefPubMedGoogle Scholar
  73. Lee Y, Manegold JE, Kim AD et al (2014) FGF signalling specifies haematopoietic stem cells through its regulation of somitic notch signalling. Nat Commun 5:5583CrossRefPubMedPubMedCentralGoogle Scholar
  74. Lessard J, Faubert A, Sauvageau G (2004) Genetic programs regulating HSC specification, maintenance and expansion. Oncogene 23:7199–7209CrossRefPubMedGoogle Scholar
  75. Leung A, Ciau-Uitz A, Pinheiro P et al (2013) Uncoupling VEGFA functions in arteriogenesis and hematopoietic stem cell specification. Dev Cell 24:144–158CrossRefPubMedPubMedCentralGoogle Scholar
  76. Li Y, Esain V, Teng L et al (2014) Inflammatory signaling regulates embryonic hematopoietic stem and progenitor cell production. Genes Dev 28:2597–2612CrossRefPubMedPubMedCentralGoogle Scholar
  77. Liao EC, Paw BH, Oates AC, Pratt SJ, Postlethwait JH, Zon LI (1998) SCL/Tal-1 transcription factor acts downstream of cloche to specify hematopoietic and vascular progenitors in zebrafish. Genes Dev 12:621–626CrossRefPubMedPubMedCentralGoogle Scholar
  78. Lim KC, Hosoya T, Brandt W et al (2012) Conditional Gata2 inactivation results in HSC loss and lymphatic mispatterning. J Clin Invest 122:3705–3717CrossRefPubMedPubMedCentralGoogle Scholar
  79. Lizama CO, Hawkins JS, Schmitt CE et al (2015) Repression of arterial genes in hemogenic endothelium is sufficient for haematopoietic fate acquisition. Nat Commun 6:7739CrossRefPubMedPubMedCentralGoogle Scholar
  80. Luis TC, Weerkamp F, Naber BA et al (2009) Wnt3a deficiency irreversibly impairs hematopoietic stem cell self-renewal and leads to defects in progenitor cell differentiation. Blood 113:546–554CrossRefPubMedGoogle Scholar
  81. Mahony CB, Fish RJ, Pasche C, Bertrand JY (2016) tfec controls the hematopoietic stem cell vascular niche during zebrafish embryogenesis. Blood 128:1336–1345CrossRefPubMedGoogle Scholar
  82. Maye P, Becker S, Kasameyer E, Byrd N, Grabel L (2000) Indian hedgehog signaling in extraembryonic endoderm and ectoderm differentiation in ES embryoid bodies. Mech Dev 94:117–132CrossRefPubMedGoogle Scholar
  83. McGrath KE, Frame JM, Fromm GJ et al (2011) A transient definitive erythroid lineage with unique regulation of the β-globin locus in the mammalian embryo. Blood 117:4600–4608CrossRefPubMedPubMedCentralGoogle Scholar
  84. Medvinsky A, Dzierzak E (1996) Definitive hematopoiesis is autonomously initiated by the AGM region. Cell 86:897–906CrossRefPubMedGoogle Scholar
  85. Moncada S, Higgs EA (2006) Nitric oxide and the vascular endothelium. Handb Exp Pharmacol 176:213–254CrossRefGoogle Scholar
  86. Monteiro R, Pinheiro P, Joseph N et al (2016) Transforming growth factor β drives Hemogenic endothelium programming and the transition to hematopoietic stem cells. Dev Cell 38:358–370CrossRefPubMedPubMedCentralGoogle Scholar
  87. Müller AM, Medvinsky A, Strouboulis J, Grosveld F, Dzierzak E (1994) Development of hematopoietic stem cell activity in the mouse embryo. Immunity 1:291–301CrossRefPubMedGoogle Scholar
  88. Mumm JS, Schroeter EH, Saxena MT et al (2000) A ligand-induced extracellular cleavage regulates gamma-secretase-like proteolytic activation of Notch1. Mol Cell 5:197–206CrossRefPubMedGoogle Scholar
  89. Murayama E, Kissa K, Zapata A et al (2006) Tracing hematopoietic precursor migration to successive hematopoietic organs during zebrafish development. Immunity 25:963–975CrossRefPubMedGoogle Scholar
  90. Murry CE, Keller G (2008) Differentiation of embryonic stem cells to clinically relevant populations: lessons from embryonic development. Cell 132:661–680CrossRefPubMedPubMedCentralGoogle Scholar
  91. North TE, de Bruijn MF, Stacy T et al (2002) Runx1 expression marks long-term repopulating hematopoietic stem cells in the midgestation mouse embryo. Immunity 16:661–672CrossRefPubMedGoogle Scholar
  92. North TE, Goessling W, Walkley CR et al (2007) Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis. Nature 447:1007–1011CrossRefPubMedPubMedCentralGoogle Scholar
  93. North TE, Goessling W, Peeters M et al (2009) Hematopoietic stem cell development is dependent on blood flow. Cell 137:736–748CrossRefPubMedPubMedCentralGoogle Scholar
  94. Ottersbach K, Dzierzak E (2005) The murine placenta contains hematopoietic stem cells within the vascular labyrinth region. Dev Cell 8:377–387CrossRefPubMedGoogle Scholar
  95. Palis J, Robertson S, Kennedy M, Wall C, Keller G (1999) Development of erythroid and myeloid progenitors in the yolk sac and embryo proper of the mouse. Development 126:5073–5084PubMedPubMedCentralGoogle Scholar
  96. Patterson LJ, Gering M, Patient R (2005) Scl is required for dorsal aorta as well as blood formation in zebrafish embryos. Blood 105:3502–3511CrossRefPubMedGoogle Scholar
  97. Pouget C, Peterkin T, Simões FC, Lee Y, Traver D, Patient R (2014) FGF signalling restricts haematopoietic stem cell specification via modulation of the BMP pathway. Nat Commun 5:5588CrossRefPubMedPubMedCentralGoogle Scholar
  98. Qian F, Zhen F, Xu J, Huang M, Li W, Wen Z (2007) Distinct functions for different scl isoforms in zebrafish primitive and definitive hematopoiesis. PLoS Biol 5:e132CrossRefPubMedPubMedCentralGoogle Scholar
  99. Ren X, Gomez GA, Zhang B, Lin S (2010) Scl isoforms act downstream of etsrp to specify angioblasts and definitive hematopoietic stem cells. Blood 115:5338–5346CrossRefPubMedPubMedCentralGoogle Scholar
  100. Richard C, Drevon C, Canto PY et al (2013) Endothelio-mesenchymal interaction controls runx1 expression and modulates the notch pathway to initiate aortic hematopoiesis. Dev Cell 24:600–611CrossRefPubMedPubMedCentralGoogle Scholar
  101. Robert-Moreno A, Guiu J, Ruiz-Herguido C et al (2008) Impaired embryonic haematopoiesis yet normal arterial development in the absence of the notch ligand Jagged1. EMBO J 27:1886–1895CrossRefPubMedPubMedCentralGoogle Scholar
  102. Ruiz-Herguido C, Guiu J, D’Altri T et al (2012) Hematopoietic stem cell development requires transient Wnt/β-catenin activity. J Exp Med 209:1457–1468CrossRefPubMedPubMedCentralGoogle Scholar
  103. Rybtsov S, Sobiesiak M, Taoudi S et al (2011) Hierarchical organization and early hematopoietic specification of the developing HSC lineage in the AGM region. J Exp Med 208:1305–1315CrossRefPubMedPubMedCentralGoogle Scholar
  104. Samokhvalov IM, Samokhvalova NI, Nishikawa S (2007) Cell tracing shows the contribution of the yolk sac to adult haematopoiesis. Nature 446:1056–1061CrossRefPubMedGoogle Scholar
  105. Sawamiphak S, Kontarakis Z, Stainier DY (2014) Interferon gamma signaling positively regulates hematopoietic stem cell emergence. Dev Cell 31:640–653CrossRefPubMedPubMedCentralGoogle Scholar
  106. Shah AN, Davey CF, Whitebirch AC, Miller AC, Moens CB (2015) Rapid reverse genetic screening using CRISPR in zebrafish. Nat Methods 12:535–540CrossRefPubMedPubMedCentralGoogle Scholar
  107. Shepard JL, Zon LI (2000) Developmental derivation of embryonic and adult macrophages. Curr Opin Hematol 7:3–8CrossRefPubMedGoogle Scholar
  108. Soma T, Yu JM, Dunbar CE (1996) Maintenance of murine long-term repopulating stem cells in ex vivo culture is affected by modulation of transforming growth factor-beta but not macrophage inflammatory protein-1 alpha activities. Blood 87:4561–4567PubMedGoogle Scholar
  109. Soza-Ried C, Hess I, Netuschil N, Schorpp M, Boehm T (2010) Essential role of c-myb in definitive hematopoiesis is evolutionarily conserved. Proc Natl Acad Sci U S A 107:17304–17308CrossRefPubMedPubMedCentralGoogle Scholar
  110. Stamatoyannopoulos G (2005) Control of globin gene expression during development and erythroid differentiation. Exp Hematol 33:259–271CrossRefPubMedPubMedCentralGoogle Scholar
  111. Sugiyama T, Kohara H, Noda M, Nagasawa T (2006) Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity 25:977–988CrossRefPubMedGoogle Scholar
  112. Sumanas S, Lin S (2006) Ets1-related protein is a key regulator of vasculogenesis in zebrafish. PLoS Biol 4:e10CrossRefPubMedGoogle Scholar
  113. Sumanas S, Gomez G, Zhao Y, Park C, Choi K, Lin S (2008) Interplay among Etsrp/ER71, Scl, and Alk8 signaling controls endothelial and myeloid cell formation. Blood 111:4500–4510CrossRefPubMedPubMedCentralGoogle Scholar
  114. Tamplin OJ, Durand EM, Carr LA et al (2015) Hematopoietic stem cell arrival triggers dynamic remodeling of the perivascular niche. Cell 160:241–252CrossRefPubMedPubMedCentralGoogle Scholar
  115. Taoudi S, Gonneau C, Moore K et al (2008) Extensive hematopoietic stem cell generation in the AGM region via maturation of VE-cadherin+CD45+ pre-definitive HSCs. Cell Stem Cell 3:99–108CrossRefPubMedGoogle Scholar
  116. Theodore LN, Hagedorn EJ, Cortes M et al (2017) Distinct roles for matrix Metalloproteinases 2 and 9 in embryonic hematopoietic stem cell emergence, migration, and niche colonization. Stem Cell Rep 8:1226–1241CrossRefGoogle Scholar
  117. Thompson MA, Ransom DG, Pratt SJ et al (1998) The cloche and spadetail genes differentially affect hematopoiesis and vasculogenesis. Dev Biol 197:248–269CrossRefPubMedGoogle Scholar
  118. Tober J, Koniski A, McGrath KE et al (2007) The megakaryocyte lineage originates from hemangioblast precursors and is an integral component both of primitive and of definitive hematopoiesis. Blood 109:1433–1441CrossRefPubMedPubMedCentralGoogle Scholar
  119. Tsai FY, Orkin SH (1997) Transcription factor GATA-2 is required for proliferation/survival of early hematopoietic cells and mast cell formation, but not for erythroid and myeloid terminal differentiation. Blood 89:3636–3643PubMedGoogle Scholar
  120. Tsai FY, Keller G, Kuo FC et al (1994) An early haematopoietic defect in mice lacking the transcription factor GATA-2. Nature 371:221–226CrossRefPubMedGoogle Scholar
  121. Walkley CR, McArthur GA, Purton LE (2005) Cell division and hematopoietic stem cells: not always exhausting. Cell Cycle 4:893–896CrossRefPubMedGoogle Scholar
  122. Wang L, Zhang P, Wei Y, Gao Y, Patient R, Liu F (2011) A blood flow-dependent klf2a-NO signaling cascade is required for stabilization of hematopoietic stem cell programming in zebrafish embryos. Blood 118:4102–4110CrossRefPubMedGoogle Scholar
  123. Warga RM, Kane DA, Ho RK (2009) Fate mapping embryonic blood in zebrafish: multi- and unipotential lineages are segregated at gastrulation. Dev Cell 16:744–755CrossRefPubMedPubMedCentralGoogle Scholar
  124. Weissman IL (2000) Stem cells: units of development, units of regeneration, and units in evolution. Cell 100:157–168CrossRefPubMedGoogle Scholar
  125. Wilkinson RN, Pouget C, Gering M et al (2009) Hedgehog and Bmp polarize hematopoietic stem cell emergence in the zebrafish dorsal aorta. Dev Cell 16:909–916CrossRefPubMedPubMedCentralGoogle Scholar
  126. Yamazaki S, Ema H, Karlsson G et al (2011) Nonmyelinating Schwann cells maintain hematopoietic stem cell hibernation in the bone marrow niche. Cell 147:1146–1158CrossRefPubMedGoogle Scholar
  127. Yoon MJ, Koo BK, Song R et al (2008) Mind bomb-1 is essential for intraembryonic hematopoiesis in the aortic endothelium and the subaortic patches. Mol Cell Biol 28:4794–4804CrossRefPubMedPubMedCentralGoogle Scholar
  128. Yu VW, Scadden DT (2016) Heterogeneity of the bone marrow niche. Curr Opin Hematol 23:331–338CrossRefPubMedGoogle Scholar
  129. Zhang Y, Jin H, Li L, Qin FX, Wen Z (2011) cMyb regulates hematopoietic stem/progenitor cell mobilization during zebrafish hematopoiesis. Blood 118:4093–4101CrossRefPubMedGoogle Scholar
  130. Zhang P, He Q, Chen D et al (2015) G protein-coupled receptor 183 facilitates endothelial-to-hematopoietic transition via Notch1 inhibition. Cell Res 25:1093–1107CrossRefPubMedPubMedCentralGoogle Scholar
  131. Zhen F, Lan Y, Yan B, Zhang W, Wen Z (2013) Hemogenic endothelium specification and hematopoietic stem cell maintenance employ distinct Scl isoforms. Development 140:3977–3985CrossRefPubMedGoogle Scholar
  132. Zhu H, Zon LI (2002) Use of zebrafish models for the analysis of human disease. Curr Protoc Hum Genet Chapter 15: unit 15.13Google Scholar
  133. Zhu C, Smith T, McNulty J et al (2011) Evaluation and application of modularly assembled zinc-finger nucleases in zebrafish. Development 138:4555–4564CrossRefPubMedPubMedCentralGoogle Scholar
  134. Zovein AC, Hofmann JJ, Lynch M et al (2008) Fate tracing reveals the endothelial origin of hematopoietic stem cells. Cell Stem Cell 3:625–636CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Faculty of Biological Science and Technology, Institute of Science and EngineeringKanazawa UniversityKakumamachi, KanazawaJapan

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