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dc.contributor.authorChandrakanthan, Vashe
dc.contributor.authorRorimpandey, Prunella
dc.contributor.authorZanini, Fabio
dc.contributor.authorChacon, Diego
dc.contributor.authorOlivier, Jake
dc.contributor.authorJoshi, Swapna
dc.contributor.authorKang, Young Chan
dc.contributor.authorKnezevic, Kathy
dc.contributor.authorHuang, Yizhou
dc.contributor.authorQiao, Qiao
dc.contributor.authorOliver, Rema A
dc.contributor.authorUnnikrishnan, Ashwin
dc.contributor.authorCarter, Daniel R
dc.contributor.authorLee, Brendan
dc.contributor.authorBrownlee, Chris
dc.contributor.authorPower, Carl
dc.contributor.authorBrink, Robert
dc.contributor.authorMendez-Ferrer, Simon
dc.contributor.authorEnikolopov, Grigori
dc.contributor.authorWalsh, William
dc.contributor.authorGottgens, Berthold
dc.contributor.authorTaoudi, Samir
dc.contributor.authorBeck, Dominik
dc.contributor.authorPimanda, John E
dc.description.abstractMouse 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.
dc.publisherNature Research
dc.rightsAttribution 4.0 International
dc.subjectCambridge Stem Cell Institute
dc.titleMesoderm-derived PDGFRA+ cells regulate the emergence of hematopoietic stem cells in the dorsal aorta.
dc.publisher.departmentDepartment of Haematology
prism.publicationNameNat Cell Biol
dc.contributor.orcidChandrakanthan, Vashe [0000-0002-4314-5029]
dc.contributor.orcidUnnikrishnan, Ashwin [0000-0001-5168-8755]
dc.contributor.orcidMendez-Ferrer, Simon [0000-0002-9805-9988]
dc.contributor.orcidGottgens, Berthold [0000-0001-6302-5705]
dc.contributor.orcidPimanda, John E [0000-0002-0509-8962]
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (203151/A/16/Z)
pubs.funder-project-idMedical Research Council (MR/S036113/1)
cam.orpheus.successWed Aug 03 09:45:59 BST 2022 - This item is covered by RRS with an embargo. The item is now published and embargo has been lifted.
pubs.licence-display-nameApollo Repository Deposit Licence Agreement

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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International