Mesoderm-derived PDGFRA+ cells regulate the emergence of hematopoietic stem cells in the dorsal aorta

Autor: Chandrakanthan, Vashe, Rorimpandey, Prunella, Zanini, Fabio, Chacon, Diego, Olivier, Jake, Joshi, Swapna, Kang, Young Chan, Knezevic, Kathy, Huang, Yizhou, Qiao, Qiao, Oliver, Rema A, Unnikrishnan, Ashwin, Carter, Daniel R, Lee, Brendan, Brownlee, Chris, Power, Carl, Brink, Robert, Mendez-Ferrer, Simon, Enikolopov, Grigori, Walsh, William, Göttgens, Berthold, Taoudi, Samir, Beck, Dominik, Pimanda, John E
Přispěvatelé: Chandrakanthan, Vashe [0000-0002-4314-5029], Unnikrishnan, Ashwin [0000-0001-5168-8755], Mendez-Ferrer, Simon [0000-0002-9805-9988], Göttgens, Berthold [0000-0001-6302-5705], Pimanda, John E [0000-0002-0509-8962], Apollo - University of Cambridge Repository
Rok vydání: 2022
Předmět:
DOI: 10.17863/cam.88080
Popis: Funder: Wellcome Trust
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.
Databáze: OpenAIRE
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