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Single-cell and spatial transcriptomics identify a macrophage population associated with skeletal muscle fibrosis.

Macrophages are essential for skeletal muscle homeostasis, but how their dysregulation contributes to the development of fibrosis in muscle disease remains unclear. Here, we used single-cell transcriptomics to determine the molecular attributes of dystrophic and healthy muscle macrophages. We identified six clusters and unexpectedly found that none corresponded to traditional definitions of M1 or M2 macrophages. Rather, the predominant macrophage signature in dystrophic muscle was characterized by high expression of fibrotic factors, galectin-3 (gal-3) and osteopontin ( Spp1 ). Spatial transcriptomics, computational inferences of intercellular communication, and in vitro assays indicated that macrophage-derived Spp1 regulates stromal progenitor differentiation. Gal-3 + macrophages were chronically activated in dystrophic muscle, and adoptive transfer assays showed that the gal-3 + phenotype was the dominant molecular program induced within the dystrophic milieu. Gal-3 + macrophages wer

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Single-cell and spatial transcriptomics identify a macrophage population associated with skeletal muscle fibrosis.

> 商业许可源文 · EUROPE_PMC · [CC-BY](https://creativecommons.org/licenses/by/)

书目信息

  • 引用：Coulis G, Jaime D, Guerrero-Juarez C, Kastenschmidt JM, Farahat PK, Nguyen Q, Pervolarakis N, McLinden K, Thurlow L, Movahedi S, Hughes BS, Duarte J, Sorn A, Montoya E, Mozaffar I, Dragan M, Othy S, Joshi T, Hans CP, Kimonis V, MacLean AL, Nie Q, Wallace LM, Harper SQ, Mozaffar T, Hogarth MW, Bhattacharya S, Jaiswal JK, Golann DR, Su Q, Kessenbrock K, Stec M, Spencer MJ, Zamudio JR, Villalta SA. (2023). Single-cell and spatial transcriptomics identify a macrophage population associated with skeletal muscle fibrosis. Science advances. PMID 37418531 · PMC10328414 · DOI 10.1126/sciadv.add9984
  • 证据类型：PRIMARY_RESEARCH
  • 主题：rna-seq、single-cell、spatial-omics
  • 被引次数（采集时）：116
  • 原始记录：[Europe PMC](https://europepmc.org/article/MED/37418531)
  • 来源许可：[CC-BY](https://creativecommons.org/licenses/by/)

    • 作者摘要（按来源许可复用）

    Macrophages are essential for skeletal muscle homeostasis, but how their dysregulation contributes to the development of fibrosis in muscle disease remains unclear. Here, we used single-cell transcriptomics to determine the molecular attributes of dystrophic and healthy muscle macrophages. We identified six clusters and unexpectedly found that none corresponded to traditional definitions of M1 or M2 macrophages. Rather, the predominant macrophage signature in dystrophic muscle was characterized by high expression of fibrotic factors, galectin-3 (gal-3) and osteopontin ( Spp1 ). Spatial transcriptomics, computational inferences of intercellular communication, and in vitro assays indicated that macrophage-derived Spp1 regulates stromal progenitor differentiation. Gal-3 + macrophages were chronically activated in dystrophic muscle, and adoptive transfer assays showed that the gal-3 + phenotype was the dominant molecular program induced within the dystrophic milieu. Gal-3 + macrophages were also elevated in multiple human myopathies. These studies advance our understanding of macrophages in muscular dystrophy by defining their transcriptional programs and reveal Spp1 as a major regulator of macrophage and stromal progenitor interactions.

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    Single-cell and spatial transcriptomics identify a macrophage population associated with skeletal muscle fibrosis. · GeniOmics