Show simple item record

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.date.accessioned2022-06-30T23:30:17Z
dc.date.available2022-06-30T23:30:17Z
dc.date.issued2022-07-28
dc.identifier.issn1465-7392
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/338646
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.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectCambridge Stem Cell Institute
dc.titleMesoderm-derived PDGFRA+ cells regulate the emergence of hematopoietic stem cells in the dorsal aorta.
dc.typeArticle
dc.publisher.departmentDepartment of Haematology
dc.date.updated2022-06-30T09:36:33Z
prism.publicationNameNat Cell Biol
dc.identifier.doi10.17863/CAM.86057
dcterms.dateAccepted2022-06-06
rioxxterms.versionofrecord10.1038/s41556-022-00955-3
rioxxterms.versionAM
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]
dc.identifier.eissn1476-4679
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.
cam.orpheus.counter2
cam.depositDate2022-06-30
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

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