Article Regulation of muscle hypertrophy through granulin Relayed communication among mesenchymal progenitors, macrophages, and satellite cells

作者全名：Zhang, Lidan; Saito, Hayato; Higashimoto, Tatsuyoshi; Kaji, Takayuki; Nakamura, Ayasa; Iwamori, Kanako; Nagano, Ryoko; Motooka, Daisuke; Okuzaki, Daisuke; Uezumi, Akiyoshi; Seno, Shigeto; Fukada, So-ichiro

作者地址：[Zhang, Lidan] Chongqing Med Univ, Ctr Med Epigenet, Sch Basic Med Sci, Chongqing 40016, Peoples R China; [Zhang, Lidan; Saito, Hayato; Higashimoto, Tatsuyoshi; Kaji, Takayuki; Nakamura, Ayasa; Iwamori, Kanako; Nagano, Ryoko; Fukada, So-ichiro] Osaka Univ, Grad Sch Pharmaceut Sci, Lab Stem Cell Regenerat & Adaptat, 1-6 Yamada Oka, Suita, Osaka 5650871, Japan; [Nagano, Ryoko] Kyushu Univ, Fac Dent Sci, Div Maxillofacial Diagnost & Surg Sci, Lab Oral Pathol, 3-1-1Maidashi, Higashi, Fukuoka 8128582, Japan; [Motooka, Daisuke; Okuzaki, Daisuke] Osaka Univ, Res Inst Microbial Dis, Genome Informat Res Ctr, Osaka 5650871, Japan; [Uezumi, Akiyoshi] Kyushu Univ, Med Inst Bioregulat, Med Res Ctr High Depth Om, Div Cell Heterogene, 3-1-1 Maidashi, Higashi, Fukuoka 8128582, Japan; [Seno, Shigeto] Osaka Univ, Grad Sch Informat Sci & Technol, Dept Bioinformat Engn, 1-5 Yamadaoka, Suita, Osaka 5650871, Japan

通信作者：Fukada, S (通讯作者)，Osaka Univ, Grad Sch Pharmaceut Sci, Lab Stem Cell Regenerat & Adaptat, 1-6 Yamada Oka, Suita, Osaka 5650871, Japan.

来源：CELL REPORTS

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001226175200001

JCR分区：Q1

影响因子：7.5

年份：2024

卷号：43

期号：4

开始页：　

结束页：　

文献类型：Article

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摘要：Skeletal muscles exert remarkable regenerative or adaptive capacities in response to injuries or mechanical loads. However, the cellular networks underlying muscle adaptation are poorly understood compared to those underlying muscle regeneration. We employed single -cell RNA sequencing to investigate the gene expression patterns and cellular networks activated in overloaded muscles and compared these results with those observed in regenerating muscles. The cellular composition of the 4 -day overloaded muscle, when macrophage infiltration peaked, closely resembled that of the 10 -day regenerating muscle. In addition to the mesenchymal progenitor -muscle satellite cell (MuSC) axis, interactome analyses or targeted depletion experiments revealed communications between mesenchymal progenitors -macrophages and macrophages-MuSCs. Furthermore, granulin, a macrophage -derived factor, inhibited MuSC differentiation, and Granulin-knockout mice exhibited blunted muscle hypertrophy due to the premature differentiation of overloaded MuSCs. These findings reveal the critical role of granulin through the relayed communications of mesenchymal progenitors, macrophages, and MuSCs in facilitating efficient muscle hypertrophy.

基金机构：NCNP [2-6]; Takeda Science Foundation; Association Francaise contre les Myopathies (AFM) [23574]; Chongqing Municipal Basic and Frontier Research Project [CSTB2023NSCQ-MSX0303]; National Natural Science Foundation of China [32300666]; CQMU Program for Youth Innovation in Future Medicine [W0169]; Research Support Project for Life Science and Drug Discovery (Basis for Supporting Innovative Drug Discovery and Life Science Research [BINDS] ) from AMED [JP23ama121054, JP23ama121052]; [22H03466]

基金资助正文：We thank Prof. Keitaro Yamanouchi, Takashi Matsuwaki (University of Tokyo) , and RIKEN Bioresource for providing the Granulin-knockout mice. This study was supported by a Grant-in-Aid for Scientific Research (B, 22H03466) (S.-i.F.) , an intramural research grant for neurological and psychiatric disorders from NCNP (2-6) , the Takeda Science Foundation, Association Francaise contre les Myopathies (AFM; 23574) (S.-i.F.) , the Chongqing Municipal Basic and Frontier Research Project (CSTB2023NSCQ-MSX0303) (L.Z.) , the National Natural Science Foundation of China (32300666) (L.Z.) , and the CQMU Program for Youth Innovation in Future Medicine (W0169) (L.Z.) . This research was partially supported by the Research Support Project for Life Science and Drug Discovery (Basis for Supporting Innovative Drug Discovery and Life Science Research [BINDS] ) from AMED under grant nos. JP23ama121054 and JP23ama121052.