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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2022-07-28

AUTHORS

Vashe Chandrakanthan, Prunella Rorimpandey, Fabio Zanini, Diego Chacon, Jake Olivier, Swapna Joshi, Young Chan Kang, Kathy Knezevic, Yizhou Huang, Qiao Qiao, Rema A. Oliver, Ashwin Unnikrishnan, Daniel R. Carter, Brendan Lee, Chris Brownlee, Carl Power, Robert Brink, Simon Mendez-Ferrer, Grigori Enikolopov, William Walsh, Berthold Göttgens, Samir Taoudi, Dominik Beck, John E. Pimanda

ABSTRACT

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. More... »

PAGES

1211-1225

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  • Journal

    TITLE

    Nature Cell Biology

    ISSUE

    8

    VOLUME

    24

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41556-022-00955-3

    DOI

    http://dx.doi.org/10.1038/s41556-022-00955-3

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1149814297

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/35902769


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