Single‐cell RNA‐seq reveals interferon‐induced guanylate‐binding proteins are linked with sarcopenia

作者：Zhi Peng, Ruoyu Zhang, Xiaolin Kuang, Yu Chen, Shiwei Niu, Yongjun Du, Di Lu, Shaobo Li, Zhaowei Teng, Sheng Lu · 发表于：Journal of Cachexia Sarcopenia and Muscle · 年份：2022 · DOI：10.1002/jcsm.13091 · 被引用次数：25 · 研究领域：Muscle Physiology and Disorders、Nutrition and Health in Aging、Cardiomyopathy and Myosin Studies

BACKGROUND: Sarcopenia is defined as an age-related progressive loss of muscle mass and/or strength. Although different factors can contribute to this disease, the underlying mechanisms remain unclear. We assessed transcriptional heterogeneity in skeletal muscles from sarcopenic and control mice at single-cell resolution. METHODS: A mouse model was established to study sarcopenic skeletal muscles. Single-cell RNA-seq was performed on tibialis anterior (TA) muscle cells collected from sarcopenic and control mice. A series of bioinformatic analyses were carried out to identify and compare different cell types under different conditions. Immunofluorescence staining and western blotting were used to validate the findings from single-cell experiments. Tube formation assays were conducted to further evaluate the effects of Gbp2 on endothelial cells during angiogenesis. RESULTS: A murine sarcopenia model was successfully established using a senescence-accelerated mouse strain (SAMP6, n = 5). Sarcopenia phenotype was induced by administration of dexamethasone (20 mg/kg) and reduced physical activity. Senescence-resistant mice strain (SAMR1) and SAMP6 strain with similar activity but injected with PBS were recruited as two control groups. As signs of sarcopenia, body weight, muscle cell counts and cross-sectional fibre area were all significantly decreased in sarcopenic mice (P value = 0.004, 0.03 and 0.035, respectively). After quality control, 13 612 TA muscle single-cell transcript...