The role of the aging microenvironment on the fate of PDGFRβ lineage cells in skeletal muscle repair
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 skel...
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| Format: | Article |
| Language: | English |
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BMC
2022-08-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-022-03072-y |
| _version_ | 1811315272534982656 |
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| author | Aiping Lu Chieh Tseng Ping Guo Zhanguo Gao Kaitlyn E. Whitney Mikhail G. Kolonin Johnny Huard |
| author_facet | Aiping Lu Chieh Tseng Ping Guo Zhanguo Gao Kaitlyn E. Whitney Mikhail G. Kolonin Johnny Huard |
| author_sort | Aiping Lu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T11:27:19Z |
| format | Article |
| id | doaj.art-3b1b7a739f9844119cb513bb085ef0cf |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-04-13T11:27:19Z |
| publishDate | 2022-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-3b1b7a739f9844119cb513bb085ef0cf2022-12-22T02:48:39ZengBMCStem Cell Research & Therapy1757-65122022-08-0113111210.1186/s13287-022-03072-yThe role of the aging microenvironment on the fate of PDGFRβ lineage cells in skeletal muscle repairAiping Lu0Chieh Tseng1Ping Guo2Zhanguo Gao3Kaitlyn E. Whitney4Mikhail G. Kolonin5Johnny Huard6Center for Regenerative and Personalized Medicine, Steadman Philippon Research InstituteM.D. Anderson Cancer Center, The University of Texas Health Science CenterCenter for Regenerative and Personalized Medicine, Steadman Philippon Research InstituteInstitute of Molecular Medicine, The University of Texas Health Science CenterCenter for Regenerative and Personalized Medicine, Steadman Philippon Research InstituteInstitute of Molecular Medicine, The University of Texas Health Science CenterCenter for Regenerative and Personalized Medicine, Steadman Philippon Research InstituteAbstract 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.https://doi.org/10.1186/s13287-022-03072-yMesenchymal stem cellsPDGFRβ lineage cellsAgingMuscle progenitor cellSkeletal muscle injuryFibrosis and fatty infiltration |
| spellingShingle | Aiping Lu Chieh Tseng Ping Guo Zhanguo Gao Kaitlyn E. Whitney Mikhail G. Kolonin Johnny Huard The role of the aging microenvironment on the fate of PDGFRβ lineage cells in skeletal muscle repair Stem Cell Research & Therapy Mesenchymal stem cells PDGFRβ lineage cells Aging Muscle progenitor cell Skeletal muscle injury Fibrosis and fatty infiltration |
| title | The role of the aging microenvironment on the fate of PDGFRβ lineage cells in skeletal muscle repair |
| title_full | The role of the aging microenvironment on the fate of PDGFRβ lineage cells in skeletal muscle repair |
| title_fullStr | The role of the aging microenvironment on the fate of PDGFRβ lineage cells in skeletal muscle repair |
| title_full_unstemmed | The role of the aging microenvironment on the fate of PDGFRβ lineage cells in skeletal muscle repair |
| title_short | The role of the aging microenvironment on the fate of PDGFRβ lineage cells in skeletal muscle repair |
| title_sort | role of the aging microenvironment on the fate of pdgfrβ lineage cells in skeletal muscle repair |
| topic | Mesenchymal stem cells PDGFRβ lineage cells Aging Muscle progenitor cell Skeletal muscle injury Fibrosis and fatty infiltration |
| url | https://doi.org/10.1186/s13287-022-03072-y |
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