Abstract
Skeletal muscle is divided into slow- and fast-type muscles, which possess distinct contractile and metabolic properties. Myogenic progenitors associated with each muscle fiber type are known to intrinsically commit to specific muscle fiber lineage during embryonic development. However, it is still unclear whether the functionality of postnatal adult myogenic cells is attributable to the muscle fiber in which they reside, and whether the characteristics of myogenic cells derived from slow- and fast-type fibers can be distinguished at the genetic level. In this study, we isolated adult satellite cells from slow- and fast-type muscle individually and observed that satellite cells from each type of muscle generated myotubes expressing myosin heavy chain isoforms similar to their original muscle, and showed different metabolic features. Notably, we discovered that slow muscle-derived cells had low potential to differentiate but high potential to self-renew compared with fast muscle-derived cells. Additionally, cell transplantation experiments of slow muscle-derived cells into fast-type muscle revealed that slow muscle-derived cells could better contribute to myofiber formation and satellite cell constitution than fast muscle-derived cells, suggesting that the recipient muscle fiber type may not affect the predetermined abilities of myogenic cells. Gene expression analyses identified T-box transcriptional factor Tbx1 as a highly expressed gene in fast muscle-derived myoblasts. Gain- and loss-of-function experiments revealed that Tbx1 modulated muscle fiber types and oxidative metabolism in myotubes, and that Tbx1 stimulated myoblast differentiation, but did not regulate myogenic cell self-renewal. Our data suggest that metabolic and myogenic properties of myogenic progenitor cells vary depending on the type of muscle from which they originate, and that Tbx1 expression partially explains the functional differences of myogenic cells derived from fast-type and slow-type muscles.
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Acknowledgements
This work was supported by a Grant-in-Aid for a Japan Society for the Promotion of Science (JSPS) Fellowship for Research Abroad (NM), JSPS KAKENHI (NM: 15H05364), the Nakatomi Foundation (NM), the Uehara Memorial Foundation (NM), a General Insurance Association of Japan medical research grant on traffic accidents (AU), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS; AA: R01 AR062142), and the Muscular Dystrophy Association (MDA; AA).
Author contributions
NM designed and performed the experiments, analyzed the data, and wrote the manuscript. AU designed the experiments and edited the manuscript. YS and ST contributed the mouse line. AA, MU, SM, YM, RT, and KS analyzed and interpreted the data.
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Motohashi, N., Uezumi, A., Asakura, A. et al. Tbx1 regulates inherited metabolic and myogenic abilities of progenitor cells derived from slow- and fast-type muscle. Cell Death Differ 26, 1024–1036 (2019). https://doi.org/10.1038/s41418-018-0186-4
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DOI: https://doi.org/10.1038/s41418-018-0186-4
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