A Twist2-dependent progenitor cell contributes to adult skeletal muscle

Ning Liu, Glynnis A. Garry, Stephen Li, Svetlana Bezprozvannaya, Efrain Sanchez-Ortiz, Beibei Chen, John M. Shelton, Priscilla Jaichander, Rhonda Bassel-Duby, Eric N. Olson

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Skeletal muscle possesses remarkable regenerative potential due to satellite cells, an injury-responsive stem cell population located beneath the muscle basal lamina that expresses Pax7. By lineage tracing of progenitor cells expressing the Twist2 (Tw2) transcription factor in mice, we discovered a myogenic lineage that resides outside the basal lamina of adult skeletal muscle. Tw2+ progenitors are molecularly and anatomically distinct from satellite cells, are highly myogenic in vitro, and can fuse with themselves and with satellite cells. Tw2+ progenitors contribute specifically to type IIb/x myofibres during adulthood and muscle regeneration, and their genetic ablation causes wasting of type IIb myofibres. We show that Tw2 expression maintains progenitor cells in an undifferentiated state that is poised to initiate myogenesis in response to appropriate cues that extinguish Tw2 expression. Tw2-expressing myogenic progenitors represent a previously unrecognized, fibre-type-specific stem cell involved in postnatal muscle growth and regeneration.

Original languageEnglish (US)
Pages (from-to)202-213
Number of pages12
JournalNature Cell Biology
Volume19
Issue number3
DOIs
StatePublished - Mar 1 2017

ASJC Scopus subject areas

  • Cell Biology

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    Liu, N., Garry, G. A., Li, S., Bezprozvannaya, S., Sanchez-Ortiz, E., Chen, B., Shelton, J. M., Jaichander, P., Bassel-Duby, R., & Olson, E. N. (2017). A Twist2-dependent progenitor cell contributes to adult skeletal muscle. Nature Cell Biology, 19(3), 202-213. https://doi.org/10.1038/ncb3477