Muscle stem cells undergo extensive clonal drift during tissue growth via meox1-mediated induction of G2 cell-cycle arrest

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dc.contributor.authorNguyen, P.D.
dc.contributor.authorGurevich, D.B.
dc.contributor.authorSonntag, C.
dc.contributor.authorHersey, L.
dc.contributor.authorAlaei, S.
dc.contributor.authorNim, H.T.
dc.contributor.authorSiegel, A.
dc.contributor.authorHall, T.E.
dc.contributor.authorRossello, F.J.
dc.contributor.authorBoyd, S.E.
dc.contributor.authorPolo, J.M.
dc.contributor.authorCurrie, P.D.
dc.date.issued2017
dc.description.abstractOrgan growth requires a careful balance between stem cell self-renewal and lineage commitment to ensure proper tissue expansion. The cellular and molecular mechanisms that mediate this balance are unresolved in most organs, including skeletal muscle. Here we identify a long-lived stem cell pool that mediates growth of the zebrafish myotome. This population exhibits extensive clonal drift, shifting from random deployment of stem cells during development to reliance on a small number of dominant clones to fuel the vast majority of muscle growth. This clonal drift requires Meox1, a homeobox protein that directly inhibits the cell-cycle checkpoint gene ccnb1. Meox1 initiates G<sub>2</sub> cell-cycle arrest within muscle stem cells, and disrupting this G<sub>2</sub> arrest causes premature lineage commitment and the resulting defects in muscle growth. These findings reveal that distinct regulatory mechanisms orchestrate stem cell dynamics during organ growth, beyond the G<sub>0</sub>/G<sub>1</sub> cell-cycle inhibition traditionally associated with maintaining tissue-resident stem cells.
dc.description.statementofresponsibilityPhong Dang Nguyen, David Baruch Gurevich, Carmen Sonntag, Lucy Hersey, Sara Alaei, Hieu Tri Nim ... al et.
dc.identifier.citationCell Stem Cell, 2017; 21(1):107-119
dc.identifier.doi10.1016/j.stem.2017.06.003
dc.identifier.issn1934-5909
dc.identifier.issn1875-9777
dc.identifier.orcidPolo, J.M. [0000-0002-2531-778X]
dc.identifier.urihttps://hdl.handle.net/2440/133640
dc.language.isoen
dc.publisherCell Press
dc.rights© 2017 Published by Elsevier Inc.
dc.source.urihttps://doi.org/10.1016/j.stem.2017.06.003
dc.subjectCell Line
dc.subjectMyoblasts
dc.subjectAnimals
dc.subjectZebrafish
dc.subjectMice
dc.subjectHomeodomain Proteins
dc.subjectZebrafish Proteins
dc.subjectCell Lineage
dc.subjectCyclin B1
dc.subjectG2 Phase Cell Cycle Checkpoints
dc.subject.meshCell Line
dc.subject.meshMyoblasts
dc.subject.meshAnimals
dc.subject.meshZebrafish
dc.subject.meshMice
dc.subject.meshHomeodomain Proteins
dc.subject.meshZebrafish Proteins
dc.subject.meshCell Lineage
dc.subject.meshCyclin B1
dc.subject.meshG2 Phase Cell Cycle Checkpoints
dc.subject.meshTranscription Factors
dc.titleMuscle stem cells undergo extensive clonal drift during tissue growth via meox1-mediated induction of G2 cell-cycle arrest
dc.typeJournal article
pubs.publication-statusPublished

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