TY - JOUR
T1 - Ribonucleotide reductase M2B in the myofibers modulates stem cell fate in skeletal muscle
AU - Chen, Wan Jing
AU - Lin, I. Hsuan
AU - Lee, Chien Wei
AU - Yoshioka, Kiyoshi
AU - Ono, Yusuke
AU - Yan, Yu Ting
AU - Yen, Yun
AU - Chen, Yi Fan
N1 - Funding Information:
The authors acknowledge the technical support (sample preparation for transmission electron microscopy) provided by the TMU Core Facility. The authors also thank the Taiwan Animal Consortium (MOST 106-2319-B-001-004) – Taiwan Mouse Clinic, which is funded by the Ministry of Science and Technology (MOST) of Taiwan, for technical support in monitoring for metabolic cage and biochemical index analyses. This work was financially supported by the “TMU Research Center of Cancer Translational Medicine” from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan. This work was supported by Ministry of Health and Welfare (Health and welfare surcharge of tobacco products grant MOHW109-TDU-B-212-134014, MOHW109-TDU-B-212-134026, MOHW109-TDU-B-212-134020 and MOHW111-TDU-B-221-014013 to Y.Y.), and by Ministry of Science and Technology (MOST-109-2321-B-038-003; MOST108-2638-E-007 -001 -MY2 to Y.Y.). This work was also supported by the Ministry of Science and Technology (grant number MOST105-2320-B-038-022-MY3 to Y.F.C.) and Taipei Medical University (grant number DP2-109-21121-01-O-02-04 to Y.F.C.).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - The balance among quiescence, differentiation, and self-renewal of skeletal muscle stem cells (MuSCs) is tightly regulated by their intrinsic and extrinsic properties from the niche. How the niche controls MuSC fate remains unclear. Ribonucleotide reductase M2B (Rrm2b) modulates MuSC quiescence/differentiation in muscle in response to injury. Rrm2b knockout in myofibers, but not in MuSCs, led to weakness of muscles, such as a loss of muscle mass and strength. After muscle injury, damaged myofibers were more efficiently repaired in the Rrm2b myofiber-specific knockout mice than the control mice, but these myofibers were thinner and showed weak functioning. Rrm2b-deleted myofibers released several myokines, which trigger MuSCs to differentiate but not re-enter the quiescent stage to replenish the stem cell pool. Overall, Rrm2b in the myofibers plays a critical role in modulating the MuSC fate by modifying the microenvironment, and it may lead to a possible strategy to treat muscle disorders.
AB - The balance among quiescence, differentiation, and self-renewal of skeletal muscle stem cells (MuSCs) is tightly regulated by their intrinsic and extrinsic properties from the niche. How the niche controls MuSC fate remains unclear. Ribonucleotide reductase M2B (Rrm2b) modulates MuSC quiescence/differentiation in muscle in response to injury. Rrm2b knockout in myofibers, but not in MuSCs, led to weakness of muscles, such as a loss of muscle mass and strength. After muscle injury, damaged myofibers were more efficiently repaired in the Rrm2b myofiber-specific knockout mice than the control mice, but these myofibers were thinner and showed weak functioning. Rrm2b-deleted myofibers released several myokines, which trigger MuSCs to differentiate but not re-enter the quiescent stage to replenish the stem cell pool. Overall, Rrm2b in the myofibers plays a critical role in modulating the MuSC fate by modifying the microenvironment, and it may lead to a possible strategy to treat muscle disorders.
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U2 - 10.1038/s41536-022-00231-w
DO - 10.1038/s41536-022-00231-w
M3 - Article
AN - SCOPUS:85135148133
SN - 2057-3995
VL - 7
JO - npj Regenerative Medicine
JF - npj Regenerative Medicine
IS - 1
M1 - 37
ER -