Pro-fibrogenic and adipogenic aspects of chronic muscle degeneration are contributed by distinct stromal cell subpopulations

Cansu Özdemir, Duygu Akçay, Diğdem Yöyen-Ermiş, Ekim Zihni Taşkıran, Rana Soylu-Kucharz, Güneş Esendağlı, Yusuf Çetin Kocaefe

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review


Chronic skeletal muscle degeneration is characterized by fiber atrophy accompanied by deposition of extracellular matrix (ECM) components and fatty infiltration. Excessive accumulation of ECM leads to fibrosis via the contribution of fibro-adipogenic precursors (FAPs). Fibrosis also accompanies disuse atrophy and sarcopenia without significant inflammation. The present study aimed to comparatively analyze heterogeneous population of FAPs during acute injury and immobilization (tenotomy and denervation). The comparative analysis was accomplished based on the following 3 stromal cell subpopulations: i) CD140a(+)/Sca1(+); ii) CD140a(+)/Sca1(-); iii) CD140a(-)/Sca1(+). RNASeq analysis was employed to characterize and compare their quiescent and activated states. Whereas CD140a(-)/Sca1(+) was the most predominant activated subpopulation in tenotomy, denervation stimulated the CD140a(+)/Sca1(+) subpopulation. Immobilization models lacked myofiber damage and exhibited a minute increase in CD45(+) cells, as compared to acute injury. Transcriptome analysis showed common and discordant regulation of ECM components, without profound proliferative activation. Herein, we suggest unique surface markers for further identification of the investigated cell subpopulations. FAP subpopulations show similar activation kinetics in an inflammatory environment but the present findings highlight the fact that inflammation may not be a prerequisite for FAP activation. Delayed proliferation kinetics indicate that signals beyond inflammation might trigger FAP activation, leading to irreversible stromal changes.

Sidor (från-till)e0288800
TidskriftPLoS ONE
StatusPublished - 2023
Externt publiceradJa

Bibliografisk information

Copyright: © 2023 Özdemir et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Ämnesklassifikation (UKÄ)

  • Reumatologi och inflammation


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