tfec controls the hematopoietic stem cell vascular niche during zebrafish embryogenesis

Mahony, Christopher B.; Fish, Richard J.; Pasche, Corentin; Bertrand, Jean

doi:10.1182/blood-2016-04-710137

Cited by 55 publications

(75 citation statements)

References 68 publications

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“…The critical role for endothelial cells in providing Kitl for developing EMPs in the YS and for (pre‐)HSCs in the AGM and FL niches is in line with endothelial cells being an important source of Kitl for mouse BM HSCs and HSCs in the zebrafish CHT , and suggests a conserved role for endothelial cells in delivering Kitl to HSCs, regardless of their developmental stage. Kitl occurs in either a soluble or a membrane‐bound form, generated by alternative splicing of a precursor RNA .…”

Section: Discussionsupporting

confidence: 53%

Kit ligand has a critical role in mouse yolk sac and aorta–gonad–mesonephros hematopoiesis

et al. 2018

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Few studies report on the in vivo requirement for hematopoietic niche factors in the mammalian embryo. Here, we comprehensively analyze the requirement for Kit ligand (Kitl) in the yolk sac and aorta–gonad–mesonephros (AGM) niche. In‐depth analysis of loss‐of‐function and transgenic reporter mouse models show that Kitl‐deficient embryos harbor decreased numbers of yolk sac erythro‐myeloid progenitor (EMP) cells, resulting from a proliferation defect following their initial emergence. This EMP defect causes a dramatic decrease in fetal liver erythroid cells prior to the onset of hematopoietic stem cell (HSC)‐derived erythropoiesis, and a reduction in tissue‐resident macrophages. Pre‐HSCs in the AGM require Kitl for survival and maturation, but not proliferation. Although Kitl is expressed widely in all embryonic hematopoietic niches, conditional deletion in endothelial cells recapitulates germline loss‐of‐function phenotypes in AGM and yolk sac, with phenotypic HSCs but not EMPs remaining dependent on endothelial Kitl upon migration to the fetal liver. In conclusion, our data establish Kitl as a critical regulator in the in vivo AGM and yolk sac endothelial niche.

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Section: Discussionsupporting

confidence: 53%

Kit ligand has a critical role in mouse yolk sac and aorta–gonad–mesonephros hematopoiesis

et al. 2018

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“…Regarding the liver as a whole, it remains an open question whether other angiocrine factors of fetal LSECs including the composition of the perivascular ECM are also involved in establishing the hematopoietic stem cell niche of the fetal liver. In this respect, studies in zebrafish have suggested that cytokines such as stem cell factor/kitlg may be involved (36). Notably, exit from the liver microvascular hematopoietic stem cell niche is mediated by adhesive properties of PLVAP expressed by LSECs between E11.5 and E15.5 (43), while it is mediated by changes in pericyte content postnatally.…”

Section: Discussionmentioning

confidence: 99%

“…While Maf awaits further study, Lmo3-deficient mice were reported to survive into adulthood and do not show any gross abnormalities (35). Tfec has recently been shown to be an endothelial transcription factor involved in shaping the fetal hematopoietic stem cell niche in zebrafish, the so-called caudal hematopoietic tissue (CHT) (36). CHT, however, does not correspond to the developing liver in mammals.…”

Section: Discussionmentioning

confidence: 99%

GATA4-dependent organ-specific endothelial differentiation controls liver development and embryonic hematopoiesis

Géraud¹,

Koch²,

Zierow³

et al. 2017

Journal of Clinical Investigation

111

133

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“…We generated mutations in tfec using a CRISPR/Cas9 approach, obtaining several alleles which displayed essentially identical phenotypes. Although tfec mutants have been generated independently [41], that report did not examine NC-related defects, focusing instead on deficiencies in hematopoiesis. As with the CRISPR-generated exon 3 allele reported by Mahony and colleagues, our mutants fail to inflate the swim bladder (which, along with the caudal hematopoietic tissue, is another site of tfec expression; [37]) and die after approximately 12 days, apparently from lack of ability to feed.…”

Section: Discussionmentioning

confidence: 99%

TheMITFparalogtfecis required in neural crest development for fate specification of the iridophore lineage from a multipotent pigment cell progenitor

Petratou

Spencer

Kelsh

et al. 2019

Preprint

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Understanding how fate specification of distinct cell-types from multipotent progenitors occurs is a fundamental question in embryology. Neural crest stem cells (NCSCs) generate extraordinarily diverse derivatives, including multiple neural, skeletogenic and pigment cell fates. Key transcription factors and extracellular signals specifying NCSC lineages remain to be identified, and we have only a little idea of how and when they function together to control fate. Zebrafish have three neural crest-derived pigment cell types, black melanocytes, light-reflecting iridophores and yellow xanthophores, which offer a powerful model for studying the molecular and cellular mechanisms of fate segregation. Mitfa has been identified as the master regulator of melanocyte fate. Here, we show that an Mitf-related transcription factor, Tfec, functions as master regulator of the iridophore fate. Surprisingly, our phenotypic analysis of tfec mutants demonstrates that Tfec also functions in the initial specification of all three pigment cell-types, although the melanocyte and xanthophore lineages recover later. We show that Mitfa represses tfec expression, revealing a likely mechanism contributing to the decision between melanocyte and iridophore fate. Our data is consistent with the long-standing proposal of a tripotent progenitor restricted to pigment cell fates. Moreover, we investigate activation, maintenance and function of tfec in multipotent NCSCs, demonstrating for the first time its role in the gene regulatory network forming and maintaining early neural crest cells. In summary, we build on our previous work to characterise the gene regulatory network governing iridophore development, establishing Tfec as the master regulator driving iridophore specification from multipotent progenitors, while shedding light on possible cellular mechanisms of progressive fate restriction.

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tfec controls the hematopoietic stem cell vascular niche during zebrafish embryogenesis

Abstract: Key Points tfec controls the expression of cytokines in the vascular niche. tfec expands HSCs in a non–cell-autonomous fashion.

Cited by 55 publications

References 68 publications

Kit ligand has a critical role in mouse yolk sac and aorta–gonad–mesonephros hematopoiesis

Kit ligand has a critical role in mouse yolk sac and aorta–gonad–mesonephros hematopoiesis

GATA4-dependent organ-specific endothelial differentiation controls liver development and embryonic hematopoiesis

TheMITFparalogtfecis required in neural crest development for fate specification of the iridophore lineage from a multipotent pigment cell progenitor

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