Muscle Stem Cells Undergo Extensive Clonal Drift during Tissue Growth via Meox1-Mediated Induction of G2 Cell-Cycle Arrest
Dang Nguyen Phong, 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
CELL STEM CELL | CELL PRESS | Published : 2017
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..View full abstract
We thank J. Visvader, G. Kardon, C. Marcelle, H. Clevers, and A. Wood for review of the manuscript. We thank A. Klein for providing the simulation codes and F. Schreiber for feedback on simulation results. This work was supported by a National Health and Medical Research Council of Australia (NHMRC) grant to P.D.C., an Australian Postgraduate Award to P.D.N., and an NHMRC Principal Research Fellowship to P.D.C. The Australian Regenerative Medicine Institute is supported by funds from the State Government of Victoria and the Australian Federal Government.