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| Status |
Public on Sep 18, 2020 |
| Title |
Myf6/MRF4 Mediated Myokine Signaling is Required for the Maintenance of the Adult Skeletal Muscle Stem Cell Pool |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
In metazoans, skeletal muscle evolved to contract and to produce force. Recent experimental evidence suggests, however, that skeletal muscle has also acquired endocrine functions and produces a vast array of myokines, but how myokine production is regulated and how they affect the resident stem cell population of the skeletal muscle is unknown. Here, we show that in adult skeletal muscle, Myf6/MRF4 is a major regulator of myokine expression. Genetic deletion of Myf6 in skeletal muscles leads to exhaustion of the muscle stem cell (MuSCs) pool in adult mice in a myokine-dependent manner but, surprisingly, does not disrupt muscle differentiation. Using ChIP-Seq and gene expression analyses of myogenic factors, we show that Myf6/MRF4 is essential for the transcriptional activation of many myokines and muscle-secreted proteins, including ligands for canonical signaling pathways such as EGFR, VEGFR and STAT3. Consequently, MuSCs from Myf6 knockout animals show impaired activation of those signaling pathways and exhibit impaired quiescence, defective self-renewal, but nevertheless undergo differentiation. Lastly, we show that induction of myokine expression during aerobic and anaerobic exercise closely correlates with Myf6 expression. Together, these findings indicate that control of myokine signaling by Myf6 is critical to maintain muscle stem cell pool in adult skeletal muscle.
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| Overall design |
ChIP-seq for Myf6 in adult mouse muscle satellite cells, and RNA-seq in WT and Myf6 KO conditions, with or without injury.
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| Contributor(s) |
Perkins TJ, Soleimani VD |
| Citation(s) |
33047485 |
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| Submission date |
Dec 14, 2018 |
| Last update date |
Dec 22, 2020 |
| Contact name |
Theodore Perkins |
| E-mail(s) |
theodore.j.perkins@gmail.com
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| Phone |
6137378899
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| Organization name |
Ottawa Hospital Research Institute
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| Department |
Regenerative Medicine Program
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| Street address |
501 Smyth Rd.
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| City |
Ottawa |
| State/province |
Ontario |
| ZIP/Postal code |
K1H8L6 |
| Country |
Canada |
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| Platforms (2) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (14)
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| Relations |
| BioProject |
PRJNA510349 |
| SRA |
SRP173606 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE123836_Injury_WT_vs_Myf6KO_DiffExpr.tsv.gz |
1.1 Mb |
(ftp)(http) |
TSV |
| GSE123836_Myf6_5d_peaks.txt.gz |
329.4 Kb |
(ftp)(http) |
TXT |
| GSE123836_WT_vs_Myf6KO_DiffExpr.tsv.gz |
1.0 Mb |
(ftp)(http) |
TSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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