Muscle Stem Cells Undergo Extensive Clonal Drift during Tissue Growth via Meox1-Mediated Induction of G2 Cell-Cycle Arrest

Phong Dang Nguyen, David Baruch Gurevich, Carmen Sonntag, Lucy Hersey, Sara Alaei , Hieu Tri Nim, Ashley Siegel, Thomas Edward Hall, Fernando Jaime Rossello, Sarah Elizabeth Boyd, Jose Maria Polo, Peter David Currie

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Organ 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 G2 cell-cycle arrest within muscle stem cells, and disrupting this G2 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 G0/G1 cell-cycle inhibition traditionally associated with maintaining tissue-resident stem cells.

Original languageEnglish
Pages (from-to)107-119.e6
Number of pages19
JournalCell Stem Cell
Volume21
Issue number1
DOIs
Publication statusPublished - 6 Jul 2017

Keywords

  • cell cycle
  • clonal drift
  • growth
  • imaging
  • skeletal muscle
  • stem cell
  • zebrafish

Cite this

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title = "Muscle Stem Cells Undergo Extensive Clonal Drift during Tissue Growth via Meox1-Mediated Induction of G2 Cell-Cycle Arrest",
abstract = "Organ 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 G2 cell-cycle arrest within muscle stem cells, and disrupting this G2 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 G0/G1 cell-cycle inhibition traditionally associated with maintaining tissue-resident stem cells.",
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Muscle Stem Cells Undergo Extensive Clonal Drift during Tissue Growth via Meox1-Mediated Induction of G2 Cell-Cycle Arrest. / Nguyen, Phong Dang; Gurevich, David Baruch; Sonntag, Carmen; Hersey, Lucy; Alaei , Sara; Nim, Hieu Tri; Siegel, Ashley; Hall, Thomas Edward; Rossello, Fernando Jaime; Boyd, Sarah Elizabeth; Polo, Jose Maria; Currie, Peter David.

In: Cell Stem Cell, Vol. 21, No. 1, 06.07.2017, p. 107-119.e6.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Hersey, Lucy

AU - Alaei , Sara

AU - Nim, Hieu Tri

AU - Siegel, Ashley

AU - Hall, Thomas Edward

AU - Rossello, Fernando Jaime

AU - Boyd, Sarah Elizabeth

AU - Polo, Jose Maria

AU - Currie, Peter David

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