Myonuclear maturation dynamics in aged and adult regenerating mouse skeletal muscle
Myonuclear maturation dynamics in aged and adult regenerating mouse skeletal muscle
Abstract Skeletal muscle cells are multinucleated syncytial cells arising from cell fusion, yet despite sharing a common cytoplasm individual myonuclei express distinct transcriptional programs. Whether individual myonuclei acquire heterogenous transcriptional states via differences in their progenitors, during differentiation, or once their anatomical position is acquired, is not known. We performed transcriptome and pseudotime analysis of single myogenic nuclei from uninjured and post-injury murine skeletal muscle to assess when myonuclear heterogeneity is acquired. Two distinct progenitors contribute to myonuclei, one a non-myogenic fibroblast subtype, and skeletal muscle stem cells the other. Both progenitors enter a single pseudotime trajectory that bifurcates as myonuclei mature into two branches segregated by myosin isoform expression and metabolic profiles, suggesting transcriptional heterogeneity is acquired as myonuclei mature. In aged skeletal muscle myogenic progenitor expansion is perturbed and nuclei from aged muscle display distinct pseudotemporal kinetics compared to nuclei from young mice. In aged mice, the inferred myogenic differentiation trajectory is delayed, altering the distribution of myogenic nuclei in pseudotime, suggesting that altered transcriptional dynamics in nuclei in aged mice may drive age-associated muscle deficits and bias myonuclei towards acquiring oxidative metabolic profiles.
Antwine Tiffany、Cutler Alicia C、Dowell Robin、Van Deusen Ashleigh、Kurland Jesse V.、Allen Mary Ann、Hall Monica、Pawlikowski Brad、Dalla Betta Nicole、Russell Alan、Olwin Bradley
Department of Molecular, Cellular and Developmental Biology, University of ColoradoDepartment of Molecular, Cellular and Developmental Biology, University of ColoradoDepartment of Molecular, Cellular and Developmental Biology, University of Colorado||BioFrontiers Institute, University of ColoradoDepartment of Molecular, Cellular and Developmental Biology, University of Colorado||Edgewise Therapeutics. 3415 Colorado AvenueDepartment of Molecular, Cellular and Developmental Biology, University of ColoradoBioFrontiers Institute, University of ColoradoDepartment of Molecular, Cellular and Developmental Biology, University of Colorado||Department of Microbiology and Cell Biology, Montana State UniversityDepartment of Molecular, Cellular and Developmental Biology, University of Colorado||Department of Pediatrics Section of Section of Hematology, Oncology, Bone Marrow Transplant, University of Colorado, Anschutz Medical CampusDepartment of Molecular, Cellular and Developmental Biology, University of ColoradoEdgewise Therapeutics. 3415 Colorado AvenueDepartment of Molecular, Cellular and Developmental Biology, University of Colorado
细胞生物学分子生物学生理学
Antwine Tiffany,Cutler Alicia C,Dowell Robin,Van Deusen Ashleigh,Kurland Jesse V.,Allen Mary Ann,Hall Monica,Pawlikowski Brad,Dalla Betta Nicole,Russell Alan,Olwin Bradley.Myonuclear maturation dynamics in aged and adult regenerating mouse skeletal muscle[EB/OL].(2025-03-28)[2025-07-16].https://www.biorxiv.org/content/10.1101/2021.07.13.452218.点此复制
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