Journal Article

Temporal single-cell sequencing analysis reveals that GPNMB-expressing macrophages potentiate muscle regeneration

Lee, Chien-Wei, Lee, Oscar Kuang-Sheng, Chen, Yu-Chuan, Ho, Jennifer Hui-Chun, Chien, Shu, Chen, Hsiao-Yun, Lin, Wei-Ting, Li, Yi-Shuan J., Chen, Yu-Fan, Lu, Li-Fan, Lin, Chia-Hao

2025

Overview

Macrophages play a crucial role in coordinating the skeletal muscle repair response, but their phenotypic diversity and the transition of specialized subsets to resolution-phase macrophages remain poorly understood. Here, to address this issue, we induced injury and performed single-cell RNA sequencing on individual cells in skeletal muscle at different time points. Our analysis revealed a distinct macrophage subset that expressed high levels of Gpnmb and that coexpressed critical factors involved in macrophage-mediated muscle regeneration, including Igf1, Mertk and Nr1h3 . Gpnmb gene knockout inhibited macrophage-mediated efferocytosis and impaired skeletal muscle regeneration. Functional studies demonstrated that GPNMB acts directly on muscle cells in vitro and improves muscle regeneration in vivo. These findings provide a comprehensive transcriptomic atlas of macrophages during muscle injury, highlighting the key role of the GPNMB macrophage subset in regenerative processes. Our findings suggest that modulating GPNMB signaling in macrophages may represent a promising avenue for future research into therapeutic strategies for enhancing skeletal muscle regeneration. GPNMB macrophages drive muscle regeneration after injury Skeletal muscle, a major tissue in our bodies, needs to heal well after injury. Researchers have found that a protein called GPNMB plays a key role in this process. Researchers used a mouse model to explore how GPNMB affects muscle repair. They injured the muscles of mice and observed changes in macrophages over time. They found that GPNMB levels increased in certain macrophages, which helped the muscle heal. They used techniques such as single-cell RNA sequencing to identify five types of macrophage involved in healing. One type, with high GPNMB levels, was crucial for muscle repair. When they removed GPNMB from mice, muscle healing was impaired. Adding GPNMB back improved healing by promoting the growth of new muscle cells. This study suggests that targeting GPNMB could facilitate the development of treatments for muscle injuries. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.

• Publisher: Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group,생화학분자생물학회
• Subject: 13/2 / 13/31 / 13/51 / 45/91 / 631/250 / 631/80 / 64/60 / 82/51 / Animals / Apoptosis / Artificial intelligence / Biomedical and Life Sciences / Biomedicine / Cells / Cytokines / Eye Proteins / Genomes / Genomics / Growth factors / Insulin-like growth factor I / Laboratory animals / Macrophages / Macrophages - metabolism / Medical Biochemistry / Melanoma / Membrane Glycoproteins - genetics / Membrane Glycoproteins - metabolism / Mice / Mice, Inbred C57BL / Mice, Knockout / Molecular Medicine / Muscle, Skeletal - injuries / Muscle, Skeletal - metabolism / Muscle, Skeletal - physiology / Musculoskeletal system / Penicillin / Regeneration - genetics / Sequence analysis / Single-Cell Analysis - methods / Skeletal muscle / Software / Stem Cells / Transcriptome / Transcriptomics / 생화학