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

EMBO Reports
Emanuele AzzoniM de Bruijn

Abstract

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 vivoAGM and yolk sac endothelial niche.

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Citations

May 15, 2020·Cellular and Molecular Life Sciences : CMLS·Valerie Wittamer, Julien Y Bertrand
Feb 13, 2020·F1000Research·Ana G Freire, Jason M Butler
Nov 6, 2020·The Journal of Experimental Medicine·Yeojin LeeLei Ding
Dec 11, 2020·Development·Giuliano FerreroValérie Wittamer
Jan 30, 2021·Frontiers in Cell and Developmental Biology·Anna CazzolaEmanuele Azzoni
Dec 8, 2020·Frontiers in Cell and Developmental Biology·Adam M HeckBrandon Hadland
Mar 9, 2021·Frontiers in Cell and Developmental Biology·Wen Hao NeoGeorges Lacaud
Jun 10, 2021·European Journal of Immunology·Iva SplichalovaDominik Filipp
Aug 17, 2021·Frontiers in Cell and Developmental Biology·Alessandro FantinChristiana Ruhrberg

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Datasets Mentioned

BETA
GSE105267

Methods Mentioned

BETA
flow cytometry
FACS
genotyping
transgenic
PCR

Software Mentioned

Subread
Zeiss Zen
IDEAS
DESeq2
MetaCore suite
IMARIS
featureCounts
STAR
Adobe Photoshop
R

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