Show simple item record

dc.contributor.authorScheele, CLGJen
dc.contributor.authorHannezo, Een
dc.contributor.authorMuraro, MJen
dc.contributor.authorZomer, Aen
dc.contributor.authorLangedijk, NSMen
dc.contributor.authorvan Oudenaarden, Aen
dc.contributor.authorSimons, Benjaminen
dc.contributor.authorvan Rheenen, Jen
dc.date.accessioned2017-03-01T08:34:16Z
dc.date.available2017-03-01T08:34:16Z
dc.date.issued2017-02-16en
dc.identifier.issn0028-0836
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/262811
dc.description.abstractDuring puberty, the mouse mammary gland develops into a highly branched epithelial network. Owing to the absence of exclusive stem cell markers, the location, multiplicity, dynamics and fate of mammary stem cells (MaSCs), which drive branching morphogenesis, are unknown. Here we show that morphogenesis is driven by proliferative terminal end buds that terminate or bifurcate with near equal probability, in a stochastic and time-invariant manner, leading to a heterogeneous epithelial network. We show that the majority of terminal end bud cells function as highly proliferative, lineage-committed MaSCs that are heterogeneous in their expression profile and short-term contribution to ductal extension. Yet, through cell rearrangements during terminal end bud bifurcation, each MaSC is able to contribute actively to long-term growth. Our study shows that the behaviour of MaSCs is not directly linked to a single expression profile. Instead, morphogenesis relies upon lineage-restricted heterogeneous MaSC populations that function as single equipotent pools in the long term.
dc.description.sponsorshipThis work was supported by an ERC consolidator grant (648804); research grants from the Dutch Organization of Scientific Research (NWO; 823.02.017), the Dutch Cancer Society (KWF; HUBR 2009 -4621), the Association for International Cancer Research (AICR; 13- 0297) (all J.v.R) ,the Wellcome Trust (grant number 098357/Z/12/Z; BDS and 110326/Z/15/Z; EH ) and equipment grants (175.010.2007.00 and 834.11.002) from the Dutch Organization of Scientific Research (NWO). EH is funded by a Junior Research Fellowship from Trinity College, Cambridge University, a Sir Henry Wellcome Fellowship from the Wellcome Trust and acknowledges the Bettencourt-Schueller Young Researcher Prize for support. CLGJS is funded by a Boehringer Ingelheim Fonds PhD Fellowship.
dc.languageengen
dc.language.isoenen
dc.publisherNature Publishing Group
dc.titleIdentity and dynamics of mammary stem cells during branching morphogenesisen
dc.typeArticle
prism.endingPage317
prism.publicationDate2017en
prism.publicationNameNatureen
prism.startingPage313
prism.volume542en
dc.identifier.doi10.17863/CAM.8101
dcterms.dateAccepted2016-12-05en
rioxxterms.versionofrecord10.1038/nature21046en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2017-02-16en
dc.contributor.orcidSimons, Benjamin [0000-0002-3875-7071]
dc.identifier.eissn1476-4687
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWELLCOME TRUST (098357/Z/12/Z)
pubs.funder-project-idMRC (MC_PC_12009)
pubs.funder-project-idWELLCOME TRUST (110326/Z/15/Z)
cam.issuedOnline2017-01-30en
rioxxterms.freetoread.startdate2017-07-30


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record