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Pro-inflammatory macrophages impair skeletal muscle regeneration in ischemic-damaged limbs by inducing precocious differentiation of satellite cells.

Publication ,  Journal Article
Southerland, KW; Xu, Y; Peters, DT; Wei, X; Lin, X; Xiang, Y; Fei, K; Olivere, LA; Morowitz, JM; Otto, J; Dai, Q; Kontos, CD; Diao, Y
Published in: bioRxiv
April 3, 2023

Chronic limb-threatening ischemia (CLTI), representing the end-stage of peripheral arterial disease (PAD), is associated with a one-year limb amputation rate of ∼15-20% and significant mortality. A key characteristic of CLTI is the failure of the innate regenerative capacity of skeletal muscle, though the underlying mechanisms remain unclear. Here, single-cell transcriptome analysis of ischemic and non-ischemic muscle from the same CLTI patients demonstrated that ischemic-damaged tissue is enriched with pro-inflammatory macrophages. Comparable results were also observed in a murine CLTI model. Importantly, integrated analyses of both human and murine data revealed premature differentiation of muscle satellite cells (MuSCs) in damaged tissue and indications of defects in intercellular signaling communication between MuSCs and their inflammatory niche. Collectively, our research provides the first single-cell transcriptome atlases of skeletal muscle from CLTI patients and murine models, emphasizing the crucial role of macrophages and inflammation in regulating muscle regeneration in CLTI through interactions with MuSCs.

Duke Scholars

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bioRxiv

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Publication Date

April 3, 2023

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United States
 

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Southerland, K. W., Xu, Y., Peters, D. T., Wei, X., Lin, X., Xiang, Y., … Diao, Y. (2023). Pro-inflammatory macrophages impair skeletal muscle regeneration in ischemic-damaged limbs by inducing precocious differentiation of satellite cells. BioRxiv. https://doi.org/10.1101/2023.04.01.535211
Southerland, Kevin W., Yueyuan Xu, Derek T. Peters, Xiaolin Wei, Xin Lin, Yu Xiang, Kaileen Fei, et al. “Pro-inflammatory macrophages impair skeletal muscle regeneration in ischemic-damaged limbs by inducing precocious differentiation of satellite cells.BioRxiv, April 3, 2023. https://doi.org/10.1101/2023.04.01.535211.
Southerland KW, Xu Y, Peters DT, Wei X, Lin X, Xiang Y, Fei K, Olivere LA, Morowitz JM, Otto J, Dai Q, Kontos CD, Diao Y. Pro-inflammatory macrophages impair skeletal muscle regeneration in ischemic-damaged limbs by inducing precocious differentiation of satellite cells. bioRxiv. 2023 Apr 3;

Published In

bioRxiv

DOI

Publication Date

April 3, 2023

Location

United States