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Synergistic effects of TGFβ2, WNT9a, and FGFR4 signals attenuate satellite cell differentiation during skeletal muscle development
- Source :
- Aging Cell
- Publication Year :
- 2018
-
Abstract
- Summary Satellite cells play a key role in the aging, generation, and damage repair of skeletal muscle. The molecular mechanism of satellite cells in these processes remains largely unknown. This study systematically investigated for the first time the characteristics of mouse satellite cells at ten different ages. Results indicated that the number and differentiation capacity of satellite cells decreased with age during skeletal muscle development. Transcriptome analysis revealed that 2,907 genes were differentially expressed at six time points at postnatal stage. WGCNA and GO analysis indicated that 1,739 of the 2,907 DEGs were mainly involved in skeletal muscle development processes. Moreover, the results of WGCNA and protein interaction analysis demonstrated that Tgfβ2, Wnt9a, and Fgfr4 were the key genes responsible for the differentiation of satellite cells. Functional analysis showed that TGFβ2 and WNT9a inhibited, whereas FGFR4 promoted the differentiation of satellite cells. Furthermore, each two of them had a regulatory relationship at the protein level. In vivo study also confirmed that TGFβ2 could regulate the regeneration of skeletal muscle, as well as the expression of WNT9a and FGFR4. Therefore, we concluded that the synergistic effects of TGFβ2, WNT9a, and FGFR4 were responsible for attenuating of the differentiation of aging satellite cells during skeletal muscle development. This study provided new insights into the molecular mechanism of satellite cell development. The target genes and signaling pathways investigated in this study would be useful for improving the muscle growth of livestock or treating muscle diseases in clinical settings.
- Subjects :
- 0301 basic medicine
Aging
Satellite Cells, Skeletal Muscle
Cellular differentiation
Biology
Muscle hypertrophy
Transcriptome
03 medical and health sciences
Mice
Transforming Growth Factor beta2
medicine
Animals
Receptor, Fibroblast Growth Factor, Type 4
skeletal muscle satellite cell
Muscle, Skeletal
Cells, Cultured
Cellular Senescence
WNT9a
Cell growth
Regeneration (biology)
TGFβ2
Skeletal muscle
Cell Differentiation
Cell Biology
Original Articles
differentiation
biology.organism_classification
Cell biology
Mice, Inbred C57BL
Wnt Proteins
030104 developmental biology
medicine.anatomical_structure
age
FGFR4
Satellite (biology)
Original Article
Signal transduction
Signal Transduction
Subjects
Details
- ISSN :
- 14749726
- Volume :
- 17
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Aging cell
- Accession number :
- edsair.doi.dedup.....3082e562e05cf76f9c76970493d3c52a