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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.

journal_name

Cell Stem Cell

journal_title

Cell stem cell

authors

Nguyen PD,Gurevich DB,Sonntag C,Hersey L,Alaei S,Nim HT,Siegel A,Hall TE,Rossello FJ,Boyd SE,Polo JM,Currie PD

doi

10.1016/j.stem.2017.06.003

subject

Has Abstract

pub_date

2017-07-06 00:00:00

pages

107-119.e6

issue

1

eissn

1934-5909

issn

1875-9777

pii

S1934-5909(17)30229-1

journal_volume

21

pub_type

杂志文章

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