Back to Search Start Over

The role of the aging microenvironment on the fate of PDGFRβ lineage cells in skeletal muscle repair

Authors :
Aiping Lu
Chieh Tseng
Ping Guo
Zhanguo Gao
Kaitlyn E. Whitney
Mikhail G. Kolonin
Johnny Huard
Source :
Stem Cell Research & Therapy, Vol 13, Iss 1, Pp 1-12 (2022)
Publication Year :
2022
Publisher :
BMC, 2022.

Abstract

Abstract Background During aging, perturbation of muscle progenitor cell (MPC) constituents leads to progressive loss of muscle mass and accumulation of adipose and fibrotic tissue. Mesenchymal stem cells (MSCs) give rise to adipocytes and fibroblasts that accumulate in injured and pathological skeletal muscle through constitutive activation of platelet-derived growth factor receptors (PDGFRs). Although the role of the PDGFRα has been widely explored, there is a paucity of evidence demonstrating the role of PDGFRβ in aged skeletal muscle. Methods In this study, we investigated the role of PDGFRβ lineage cells in skeletal muscle during aging by using Cre/loxP lineage tracing technology. The PDGFR-Cre mice were crossed with global double-fluorescent Cre reporter mice (mTmG) that indelibly marks PDGFRβ lineage cells. Those cells were analyzed and compared at different ages in the skeletal muscle of the mice. Results Our results demonstrated that PDGFRβ lineage cells isolated from the muscles of young mice are MPC-like cells that exhibited satellite cell morphology, expressed Pax7, and undergo myogenic differentiation producing myosin heavy chain expressing myotubes. Conversely, the PDGFRβ lineage cells isolated from muscles of old mice displayed MSC morphology with a reduced myogenic differentiation potential while expressing adipogenic and fibrotic differentiation markers. PDGFRβ lineage cells also gave rise to newly regenerated muscle fibers in young mice after muscle injury, but their muscle regenerative process is reduced in old mice. Conclusions Our data suggest that PDGFRβ lineage cells function as MPCs in young mice, while the same PDGFRβ lineage cells from old mice undergo a fate switch participating in adipose and fibrotic tissue infiltration in aged muscle. The inhibition of fate-switching in PDGFRβ lineage cells may represent a potential approach to prevent fibrosis and fatty infiltration in skeletal muscle during the aging process.

Details

Language :
English
ISSN :
17576512
Volume :
13
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Stem Cell Research & Therapy
Publication Type :
Academic Journal
Accession number :
edsdoj.3b1b7a739f9844119cb513bb085ef0cf
Document Type :
article
Full Text :
https://doi.org/10.1186/s13287-022-03072-y