Mesoderm-derived PDGFRA(+) cells regulate the emergence of hematopoietic stem cells in the dorsal aorta
Publication Year 2022-07-28,Volume 24,Issue #8,Page 1211-1225
Journal Title
Nature Cell Biology
Mouse haematopoietic stem cells (HSCs) first emerge at embryonic day 10.5 (E10.5), on the ventral surface of the dorsal aorta, by endothelial-to-haematopoietic transition. We investigated whether mesenchymal stem cells, which provide an essential niche for long-term HSCs (LT-HSCs) in the bone marrow, reside in the aorta-gonad-mesonephros and contribute to the development of the dorsal aorta and endothelial-to-haematopoietic transition. Here we show that mesoderm-derived PDGFRA(+) stromal cells (Mesp1(der) PSCs) contribute to the haemogenic endothelium of the dorsal aorta and populate the E10.5-E11.5 aorta-gonad-mesonephros but by E13.5 were replaced by neural-crest-derived PSCs (Wnt1(der) PSCs). Co-aggregating non-haemogenic endothelial cells with Mesp1(der) PSCs but not Wnt1(der) PSCs resulted in activation of a haematopoietic transcriptional programme in endothelial cells and generation of LT-HSCs. Dose-dependent inhibition of PDGFRA or BMP, WNT and NOTCH signalling interrupted this reprogramming event. Together, aorta-gonad-mesonephros Mesp1(der) PSCs could potentially be harnessed to manufacture LT-HSCs from endothelium.
WEHI Research Division(s)
Epigenetics And Development
PubMed ID
Open Access at Publisher's Site
Terms of Use/Rights Notice
Refer to copyright notice on published article.

Creation Date: 2022-08-08 09:15:47
Last Modified: 2022-08-12 09:58:39
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