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dc.contributor.authorAndersen, Marianne Stemannen
dc.contributor.authorHannezo, Edouarden
dc.contributor.authorUlyanchenko, Svetlanaen
dc.contributor.authorEstrach, Solineen
dc.contributor.authorAntoku, Yasukoen
dc.contributor.authorPisano, Sabrinaen
dc.contributor.authorBoonekamp, Kim Een
dc.contributor.authorSendrup, Sarahen
dc.contributor.authorMaimets, Marttien
dc.contributor.authorPedersen, Marianne Terndrupen
dc.contributor.authorJohansen, Jens Ven
dc.contributor.authorClement, Ditte Len
dc.contributor.authorFeral, Chloe Cen
dc.contributor.authorSimons, Benjaminen
dc.contributor.authorJensen, Kim Ben
dc.date.accessioned2019-07-24T23:31:18Z
dc.date.available2019-07-24T23:31:18Z
dc.date.issued2019-08en
dc.identifier.issn1465-7392
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/294890
dc.description.abstractThe sebaceous gland (SG) is an essential component of the skin, and SG dysfunction is debilitating1, 2. Yet, the cellular bases for its origin, development and subsequent maintenance remain poorly understood. Here, we apply large-scale quantitative fate mapping to define the patterns of cell fate behaviour during SG development and maintenance. We show that the SG develops from a defined number of lineage-restricted progenitors that undergo a programme of independent and stochastic cell fate decisions. Following an expansion phase, equipotent progenitors transition into a phase of homeostatic turnover, which is correlated with changes in the mechanical properties of the stroma and spatial restrictions on gland size. Expression of the oncogene KrasG12D results in a release from these constraints and unbridled gland expansion. Quantitative clonal fate analysis reveals that, during this phase, the primary effect of the Kras-oncogene is to drive a constant fate bias with little effect on cell division rates. These findings provide insight into the developmental programme of the SG, as well as the mechanisms that drive tumour progression and gland dysfunction.
dc.description.sponsorshipWellcome Trust Royal Society
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherNature Publishing Group
dc.rightsAll rights reserved
dc.rights.uri
dc.subjectStem Cellsen
dc.subjectAnimalsen
dc.subjectMice, Transgenicen
dc.subjectDisease Progressionen
dc.subjectCell Proliferationen
dc.subjectGene Expression Regulation, Developmentalen
dc.subjectHomeostasisen
dc.titleTracing the cellular dynamics of sebaceous gland development in normal and perturbed states.en
dc.typeArticle
prism.endingPage932
prism.issueIdentifier8en
prism.publicationDate2019en
prism.publicationNameNature cell biologyen
prism.startingPage924
prism.volume21en
dc.identifier.doi10.17863/CAM.41979
dcterms.dateAccepted2019-06-18en
rioxxterms.versionofrecord10.1038/s41556-019-0362-xen
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2019-08en
dc.contributor.orcidAndersen, Marianne Stemann [0000-0001-6751-5453]
dc.contributor.orcidHannezo, Edouard [0000-0001-6005-1561]
dc.contributor.orcidUlyanchenko, Svetlana [0000-0003-3124-9178]
dc.contributor.orcidEstrach, Soline [0000-0003-2088-5988]
dc.contributor.orcidPisano, Sabrina [0000-0002-2452-4736]
dc.contributor.orcidMaimets, Martti [0000-0001-7343-2769]
dc.contributor.orcidPedersen, Marianne Terndrup [0000-0003-3808-0352]
dc.contributor.orcidFeral, Chloe C [0000-0001-9756-2082]
dc.contributor.orcidSimons, Benjamin [0000-0002-3875-7071]
dc.contributor.orcidJensen, Kim B [0000-0001-6569-1664]
dc.identifier.eissn1476-4679
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWELLCOME TRUST (098357/Z/12/Z)
pubs.funder-project-idRoyal Society (RP/R1/180165)
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) Societal Challenges (668294-2 INTENS)
pubs.funder-project-idMRC (MC_PC_12009)
cam.orpheus.successThu Jan 30 10:41:35 GMT 2020 - Embargo updated*
rioxxterms.freetoread.startdate2020-02-29


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