Repository logo
 

Hyaluronic acid-GPRC5C signalling promotes dormancy in haematopoietic stem cells.

Simple item page
cam.depositDate2022-06-21
cam.issuedOnline2022-06-20
cam.orpheus.success2022-06-21 - Embargo set during processing via Fast-track
dc.contributor.authorZhang, Yu Wei
dc.contributor.authorMess, Julian
dc.contributor.authorAizarani, Nadim
dc.contributor.authorMishra, Pankaj
dc.contributor.authorJohnson, Carys
dc.contributor.authorRomero-Mulero, Mari Carmen
dc.contributor.authorRettkowski, Jasmin
dc.contributor.authorSchönberger, Katharina
dc.contributor.authorObier, Nadine
dc.contributor.authorJäcklein, Karin
dc.contributor.authorWoessner, Nadine M
dc.contributor.authorLalioti, Maria-Eleni
dc.contributor.authorVelasco-Hernandez, Talia
dc.contributor.authorSikora, Katarzyna
dc.contributor.authorWäsch, Ralph
dc.contributor.authorLehnertz, Bernhard
dc.contributor.authorSauvageau, Guy
dc.contributor.authorManke, Thomas
dc.contributor.authorMenendez, Pablo
dc.contributor.authorWalter, Sebastian Gottfried
dc.contributor.authorMinguet, Susana
dc.contributor.authorLaurenti, Elisa
dc.contributor.authorGünther, Stefan
dc.contributor.authorGrün, Dominic
dc.contributor.authorCabezas-Wallscheid, Nina
dc.contributor.orcidLaurenti, Elisa [0000-0002-9917-9092]
dc.contributor.orcidCabezas-Wallscheid, Nina [0000-0003-0870-0530]
dc.date.accessioned2022-06-21T23:31:19Z
dc.date.available2022-06-21T23:31:19Z
dc.date.issued2022-06-20
dc.date.updated2022-06-21T10:30:00Z
dc.description.abstractBone marrow haematopoietic stem cells (HSCs) are vital for lifelong maintenance of healthy haematopoiesis. In inbred mice housed in gnotobiotic facilities, the top of the haematopoietic hierarchy is occupied by dormant HSCs, which reversibly exit quiescence during stress. Whether HSC dormancy exists in humans remains debatable. Here, using single-cell RNA sequencing, we show a continuous landscape of highly purified human bone marrow HSCs displaying varying degrees of dormancy. We identify the orphan receptor GPRC5C, which enriches for dormant human HSCs. GPRC5C is also essential for HSC function, as demonstrated by genetic loss- and gain-of-function analyses. Through structural modelling and biochemical assays, we show that hyaluronic acid, a bone marrow extracellular matrix component, preserves dormancy through GPRC5C. We identify the hyaluronic acid-GPRC5C signalling axis controlling the state of dormancy in mouse and human HSCs.
dc.identifier.doi10.17863/CAM.85693
dc.identifier.eissn1476-4679
dc.identifier.issn1465-7392
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/338285
dc.language.isoeng
dc.publisherSpringer Science and Business Media LLC
dc.publisher.departmentDepartment of Haematology
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleHyaluronic acid-GPRC5C signalling promotes dormancy in haematopoietic stem cells.
dc.typeArticle
dcterms.dateAccepted2022-05-02
prism.publicationNameNat Cell Biol
pubs.funder-project-idWellcome Trust (203151/Z/16/Z)
pubs.funder-project-idWellcome Trust (107630/Z/15/Z)
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/P002293/1)
pubs.licence-display-nameApollo Repository Deposit Licence Agreement
pubs.licence-identifierapollo-deposit-licence-2-1
rioxxterms.typeJournal Article/Review
rioxxterms.versionAM
rioxxterms.versionofrecord10.1038/s41556-022-00931-x

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
NCB-C45459B_MC_1650478946_85.docx
Size:
212.34 KB
Format:
Unknown data format
Description:
Accepted version
Licence
https://creativecommons.org/licenses/by/4.0/
Download

Collections

Cambridge University Research Outputs