Migratory path of definitive hematopoietic stem/progenitor cells during zebrafish development

Abstract

The development of vertebrate definitive hematopoiesis is featured by temporally and spatially dynamic distribution of hematopoietic stem/progenitor cells (HSPCs). It is proposed that the migration of definitive HSPCs, at least in part, accounts for this unique characteristic; however, compelling in vivo lineage evidence is still lacking. Here we present an in vivo analysis to delineate the migration route of definitive HSPCs in the early zebrafish embryo. Cell-marking analysis was able to first map definitive HSPCs to the ventral wall of dorsal aorta (DA). These cells were subsequently found to migrate to a previously unappreciated organ, posterior blood island (PBI), located between the caudal artery and caudal vein, and finally populate the kidney, the adult hematopoietic organ. IntroductionThe ontogeny of vertebrate hematopoietic system is characterized by 2 phases of development: an early transitory primitive wave generating only primitive erythrocytes and some myeloid cells, and a definitive wave that initiates late and produces all the mature blood lineages (erythroid, myeloid, and lymphoid). [1][2][3][4] In vertebrates, the first hematopoietic activity can be identified in an extra-embryonic location: yolk sac in mice and chickens, or ventral blood island (VBI) in amphibians, leading to the hypothesis that yolk sac/VBI is the sole source of hematopoietic cells, which will in turn populate downstream hematopoietic compartments. 5 However, the singular hematopoietic origin from yolk sac/VBI is challenged by substantial evidence from experiments with various species that reveals another evolutionary conserved intraembryonic hematopoietic site: the para-aortic splanchnopleurae (pSP) and later referred as aorta-gonad-mesonephros (AGM). [6][7][8][9][10][11] Hence, it is currently believed that yolk sac/VBI mainly supports primitive hematopoiesis, whereas definitive hematopoiesis is autonomously initiated, at least in part, in the pSP/AGM region.The journey of definitive HSPCs is best characterized both temporally and spatially in mice. 4 Although multipotential hematopoietic progenitor cells revealed by in vitro colony assays, injection into yolk sac cavity, transplantation into fetal liver of newborn mice or reconstitution of immunodeficient mice, can be detected in the pSP/AGM region and yolk sac at earlier developmental stages, 12-15 the first definitive HSPCs, defined as cells fully competent to provide long-term reconstitution of irradiated adult recipients, emerge in the pSP/AGM region at embryonic day (E) 10.5. 6,9,11 Subsequently, at around E11.0, definitive HSPC activity can be found in yolk sac. 6,9,11 Recently, placenta is recognized as another embryonic reservoir from E10.5 for definitive HSPCs operation. 16,17 However, the cellular origin of definitive HSPCs in yolk sac and placenta and their contribution to adult hematopoiesis are not clear. From E11.5, fetal liver begins to be populated by definitive HSPCs and serves as the main site that supports hematopoietic expansion and differentiation dur...

Genetic control of hematopoietic development in Xenopus and zebrafish

“…At least partly via the circulation, these HSCs migrate and colonize a recently discovered hematopoietic organ, the caudal hematopoietic tissue (CHT), which is believed to be functionally equivalent to the mammalian fetal liver (Murayama et al, 2006). HSCs expand in the CHT and some of them differentiate into erythrocytes and myeloid cells while others further migrate to the thymus and the kidney, the main hematopoietic organ in adult fish (Jin et al, 2007;Murayama et al, 2006). In addition, recent work provides evidence for a novel migration route in which DA-derived CD41+cmyb+ cells colonize the zebrafish kidney by migrating along the pronephric tubules (Bertrand et al, 2008).…”

Regulation of Stem Cells in the Zebra Fish Hematopoietic System

“…The CHT is similar to mouse placenta or fetal liver, and developing lymphoid and myeloid cells in this region can be identified by markers such as c-myb, scl, runx1, and ikaros (Murayama et al 2006;Zhang and Rodaway 2007). Thymic immigrants differentiate into rag1 + lymphoid cells (Murayama et al 2006;Jin et al 2007;Kissa et al 2008). The kidney is the adult hematopoietic organ in zebra fish equivalent to mammalian bone marrow, and like the CHT, c-myb, scl, runx1, and ikaros are expressed in this region (Murayama et al 2006;Jin et al 2007).…”

“…These AGM cells subsequently colonize the caudal hematopoietic tissue (CHT), an expansion of the PBI, as well as the thymus and kidney (Murayama et al 2006;Jin et al 2007;Kissa et al 2008).…”

“…Live imaging of cells labeled with green fluorescent protein (GFP) driven by HSC-specific promoters, such as CD41 and c-myb, and caged fluorescein-dextran cell-tracing experiments have shown that HSCs from the AGM region migrate to colonize the CHT, thymus, and pronephros (Murayama et al 2006;Jin et al 2007;Zhang and Rodaway 2007;Bertrand et al 2008;Kissa et al 2008). CD41 marks HSCs in the mouse (Mitjavila-Garcia et al 2002;Ferkowicz et al 2003;Mikkola et al 2003).…”

“…Thymic immigrants differentiate into rag1 + lymphoid cells (Murayama et al 2006;Jin et al 2007;Kissa et al 2008). The kidney is the adult hematopoietic organ in zebra fish equivalent to mammalian bone marrow, and like the CHT, c-myb, scl, runx1, and ikaros are expressed in this region (Murayama et al 2006;Jin et al 2007). Within the kidney marrow, HSCs reside adjacent to renal tubule epithelial cells (Kobayashi et al 2008).…”