Mesoderm-derived PDGFRA+ cells regulate the emergence of hematopoietic stem cells in the dorsal aorta.
Kang, Young Chan
Oliver, Rema A
Carter, Daniel R
Nat Cell Biol
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Chandrakanthan, V., Rorimpandey, P., Zanini, F., Chacon, D., Olivier, J., Joshi, S., Kang, Y. C., et al. (2022). Mesoderm-derived PDGFRA+ cells regulate the emergence of hematopoietic stem cells in the dorsal aorta.. Nat Cell Biol https://doi.org/10.1038/s41556-022-00955-3
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 (Mesp1der 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 (Wnt1der PSCs). Co-aggregating non-haemogenic endothelial cells with Mesp1der PSCs but not Wnt1der 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 Mesp1der PSCs could potentially be harnessed to manufacture LT-HSCs from endothelium.
Cambridge Stem Cell Institute
Wellcome Trust (203151/A/16/Z)
Medical Research Council (MR/S036113/1)
External DOI: https://doi.org/10.1038/s41556-022-00955-3
This record's URL: https://www.repository.cam.ac.uk/handle/1810/338646
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/