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https://hdl.handle.net/2440/133640
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Type: | Journal article |
Title: | Muscle stem cells undergo extensive clonal drift during tissue growth via meox1-mediated induction of G2 cell-cycle arrest |
Author: | Nguyen, P.D. Gurevich, D.B. Sonntag, C. Hersey, L. Alaei, S. Nim, H.T. Siegel, A. Hall, T.E. Rossello, F.J. Boyd, S.E. Polo, J.M. Currie, P.D. |
Citation: | Cell Stem Cell, 2017; 21(1):107-119 |
Publisher: | Cell Press |
Issue Date: | 2017 |
ISSN: | 1934-5909 1875-9777 |
Statement of Responsibility: | Phong Dang Nguyen, David Baruch Gurevich, Carmen Sonntag, Lucy Hersey, Sara Alaei, Hieu Tri Nim ... al et. |
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 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. |
Keywords: | Cell Line Myoblasts Animals Zebrafish Mice Homeodomain Proteins Zebrafish Proteins Cell Lineage Cyclin B1 G2 Phase Cell Cycle Checkpoints |
Rights: | © 2017 Published by Elsevier Inc. |
DOI: | 10.1016/j.stem.2017.06.003 |
Published version: | http://dx.doi.org/10.1016/j.stem.2017.06.003 |
Appears in Collections: | Zoology publications |
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