Defining Lineage Potential and Fate Behavior of Precursors during Pancreas Development.

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cam.issuedOnline2018-07-26
dc.contributor.authorSznurkowska, Magdalena K
dc.contributor.authorHannezo, Edouard
dc.contributor.authorAzzarelli, Roberta
dc.contributor.authorRulands, Steffen
dc.contributor.authorNestorowa, Sonia
dc.contributor.authorHindley, Christopher J
dc.contributor.authorNichols, Jennifer
dc.contributor.authorGöttgens, Berthold
dc.contributor.authorHuch, Meritxell
dc.contributor.authorPhilpott, Anna
dc.contributor.authorSimons, Benjamin D
dc.contributor.orcidRulands, Steffen [0000-0001-6398-1553]
dc.contributor.orcidNichols, Jennifer [0000-0002-8650-1388]
dc.contributor.orcidGottgens, Berthold [0000-0001-6302-5705]
dc.contributor.orcidHuch Ortega, Meritxell [0000-0002-1545-5265]
dc.contributor.orcidPhilpott, Anna [0000-0003-3789-2463]
dc.contributor.orcidSimons, Benjamin [0000-0002-3875-7071]
dc.date.accessioned2018-09-20T12:05:53Z
dc.date.available2018-09-20T12:05:53Z
dc.date.issued2018-08-06
dc.description.abstractPancreas development involves a coordinated process in which an early phase of cell segregation is followed by a longer phase of lineage restriction, expansion, and tissue remodeling. By combining clonal tracing and whole-mount reconstruction with proliferation kinetics and single-cell transcriptional profiling, we define the functional basis of pancreas morphogenesis. We show that the large-scale organization of mouse pancreas can be traced to the activity of self-renewing precursors positioned at the termini of growing ducts, which act collectively to drive serial rounds of stochastic ductal bifurcation balanced by termination. During this phase of branching morphogenesis, multipotent precursors become progressively fate-restricted, giving rise to self-renewing acinar-committed precursors that are conveyed with growing ducts, as well as ductal progenitors that expand the trailing ducts and give rise to delaminating endocrine cells. These findings define quantitatively how the functional behavior and lineage progression of precursor pools determine the large-scale patterning of pancreatic sub-compartments.
dc.description.sponsorshipWellcome Trust
dc.format.mediumPrint-Electronic
dc.identifier.doi10.17863/CAM.27884
dc.identifier.eissn1878-1551
dc.identifier.issn1534-5807
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/280514
dc.languageeng
dc.publisherElsevier BV
dc.publisher.urlhttp://dx.doi.org/10.1016/j.devcel.2018.06.028
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectacini
dc.subjectbranching morphogenesis
dc.subjectdevelopment
dc.subjectdifferentiation
dc.subjectducts
dc.subjectislets
dc.subjectpancreas
dc.subjectspecification
dc.subjecttubulogenesis
dc.subjectAcinar Cells
dc.subjectAnimals
dc.subjectCell Differentiation
dc.subjectCell Lineage
dc.subjectCell Proliferation
dc.subjectEndocrine Cells
dc.subjectGene Expression Regulation, Developmental
dc.subjectMorphogenesis
dc.subjectOrganogenesis
dc.subjectPancreas
dc.subjectStem Cells
dc.titleDefining Lineage Potential and Fate Behavior of Precursors during Pancreas Development.
dc.typeArticle
dcterms.dateAccepted2018-06-29
prism.endingPage375.e5
prism.issueIdentifier3
prism.publicationDate2018
prism.publicationNameDev Cell
prism.startingPage360
prism.volume46
pubs.funder-project-idWellcome Trust (098357/Z/12/Z)
pubs.funder-project-idMRC (1514251)
pubs.funder-project-idMedical Research Council (MR/K018329/1)
pubs.funder-project-idWellcome Trust (097922/Z/11/Z)
pubs.funder-project-idMedical Research Council (MC_PC_12009)
pubs.funder-project-idWellcome Trust (110326/Z/15/Z)
pubs.funder-project-idWellcome Trust (104151/Z/14/Z)
pubs.funder-project-idMedical Research Council (MR/M008975/1)
rioxxterms.licenseref.startdate2018-08
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1016/j.devcel.2018.06.028
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