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bioRxiv · 10.1101/2023.12.12.571148

Single-cell RNAseq reveals the pro-regenerative role of senescent FAPs in muscle regeneration

Chen, C.·Saclier, M.·Chantrel, J.·Mella, S.·Chiche, A.·Li, H.
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Abstract

Muscle regeneration is associated with transient induction of cellular senescence. However, the role of senescence in muscle regeneration of young mice remains unclear. Using a mouse model deficient in both Cdkn1a and Cdkn2a, we find that a marked reduction in senescent cells correlates with delayed muscle regeneration. Single-cell RNA sequencing reveals a heterogeneous senescence program composing of multiple cell types. Notably, senescent fibro-adipogenic progenitors (FAPs) upregulate Mcl-1 to acquire apoptosis resistance. Moreover, removing senescent FAPs using a Mcl-1 inhibitor S63845 impairs muscle regeneration. Furthermore, we find that senescent FAPs promotes myogenic differentiation in a paracrine manner. Hence, these results highlight the beneficial role of senescent stromal cells in supporting muscle regeneration.

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Chen, C., Saclier, M., Chantrel, J., Mella, S., Chiche, A., Li, H.. 2023-12-13. Single-cell RNAseq reveals the pro-regenerative role of senescent FAPs in muscle regeneration. https://doi.org/10.1101/2023.12.12.571148

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