{
  "abstract": "Skeletal muscle is composed of heterogeneous myofiber types and non-myocyte populations. Myopathies occur in many diseases, but the mechanisms driving these pathologies remain largely unknown, partly because conventional approaches cannot link histopathological features to molecular states at single-fiber resolution. To address this challenge, we brought histopathology and spatial transcriptomics together by applying high-resolution Seq-Scope technology to a mouse model of mTORC1 hyperactivation. Cross-sections from the extensor digitorum longus (EDL) and soleus (SOL), two muscles with distinct fiber-type compositions, were profiled to determine how transcriptome changes are linked to histopathological outcomes. mTORC1 hyperactivation elicited distinct, fiber type–dependent pathological programs. Type I and IIa fibers were largely resistant to mTORC1-induced pathology, exhibiting relatively limited morphological alterations. In contrast, type IIx fibers diverged into opposing fates: in SOL, they underwent abnormal enlargement associated with sustained growth signaling, cytoskeletal remodeling, and impaired proteostasis; in EDL, they developed basophilia associated with increased RNA content and lipid-, oxidative-, and nucleotide metabolism–related signatures. Within EDL, type IIb fibers displayed heterogeneity with discrete transcriptional states. Non-myocytic populations, including macrophages and fibroblasts, accumulated preferentially in SOL, forming a fibrotic microenvironment associated with inflammation, remodeling, and hypertrophy. These findings provide a link between histopathological phenotypes and molecular states at single-fiber resolution.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Molecular & Integrative Physiology and",
    "Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jer-En Hsu"
    },
    {
      "affs": [
        0
      ],
      "name": "Qingyang Zhao"
    },
    {
      "affs": [
        1
      ],
      "name": "Weiqiu Cheng"
    },
    {
      "affs": [
        1
      ],
      "name": "Hyun Min Kang"
    },
    {
      "affs": [
        0
      ],
      "name": "Susan V. Brooks",
      "orcid": "0000-0003-1954-967X"
    },
    {
      "affs": [
        0
      ],
      "name": "Myungjin Kim"
    },
    {
      "affs": [
        0
      ],
      "name": "Jun Hee Lee"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9q01ps9vgfr5d.bib",
  "cited_by": 0,
  "doi": "10.1172/jci.insight.203167",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13726413/",
  "id": "9q01ps9vgfr5d",
  "issns": [
    "2379-3708"
  ],
  "landing_url": "https://doi.org/10.1172/jci.insight.203167",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "1312|Muscle Physiology and Disorders"
    ]
  ],
  "openalex": "W4417117207",
  "pdf_url": "http://insight.jci.org/articles/view/203167/files/pdf",
  "pmcid": "PMC13726413",
  "pmid": "42623145",
  "published": "2026-08-20",
  "publisher": "American Society for Clinical Investigation",
  "ris": "https://research.draconitic.com/paper/9q01ps9vgfr5d.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T12:22:46Z",
      "native_id": "PMC13726413",
      "source": "pmc",
      "url": "https://doi.org/10.1172/jci.insight.203167"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Muscle Physiology and Disorders",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Histopathology and spatial transcriptomics jointly map myofiber-specific pathological programs in mTORC1-driven myopathy",
  "title_text": "Histopathology and spatial transcriptomics jointly map myofiber-specific pathological programs in mTORC1-driven myopathy",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:22:23Z",
  "url": "https://research.draconitic.com/paper/9q01ps9vgfr5d",
  "venue": "JCI Insight",
  "versions": []
}