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Updated: Aug 12, 2025
09:19
Single Myofiber Culture Assay for the Assessment of Adult Muscle Stem Cell Functionality Ex Vivo
Published on: February 15, 2021
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The m6A reader YTHDC1 regulates muscle stem cell proliferation via PI4K-Akt-mTOR signalling
Jin Liu1, Hongna Zuo1, Ziliu Wang1
1Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Jinan University, Guangzhou, China.
Cell Proliferation
|February 1, 2023
Summary
The m6A reader Ythdc1 is crucial for muscle stem cell regeneration. Its absence prevents muscle stem cells from activating, impacting skeletal muscle repair.
Area of Science:
- Molecular Biology
- Cell Biology
- Developmental Biology
Background:
- Muscle stem cells are vital for skeletal muscle maintenance and repair.
- RNA N6-methyladenosine (m6A) modifications are known to influence muscle development and regeneration.
- The specific m6A readers regulating mammalian muscle stem cells remain largely uncharacterized.
Purpose of the Study:
- To identify the m6A reader regulating mammalian muscle stem cells.
- To elucidate the mechanism by which this reader controls muscle stem cell function.
- To understand the role of m6A readers in adult tissue regeneration.
Main Methods:
- Investigated the role of Ythdc1 in mouse skeletal muscle regeneration.
- Analyzed muscle stem cell proliferation and quiescence exit in Ythdc1-deficient mice.
- Examined the molecular mechanism involving Ythdc1, m6A-modified mRNAs (Pi4k2a, Pi4kb), and PI4K-Akt-mTOR signaling.
Main Results:
- Ythdc1 was found to be indispensable for mouse skeletal muscle regeneration and muscle stem cell proliferation.
- Ythdc1 deficiency caused muscle stem cells to remain quiescent.
- Ythdc1 regulates the alternative splicing of Pi4k2a and Pi4kb mRNAs, impacting PI4K-Akt-mTOR signaling and phosphatidylinositol (PI) 3,4,5-trisphosphate levels.
Conclusions:
- Ythdc1 is a critical regulator of muscle stem cell activation and proliferation.
- The Ythdc1-mediated regulation of PI4K-Akt-mTOR signaling is essential for stem cell exit from quiescence.
- This study links dynamic RNA methylation to stem cell proliferation and adult tissue regeneration via PI4K-Akt-mTOR pathway.
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