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FEBS Journal· 2026Q1

High‐resolution spatial transcriptomic atlas of mouse soleus muscle: Unveiling single cell and subcellular heterogeneity in health and denervation

Jer-En Hsu, Lloyd Ruiz, Yongha Hwang, Steve D. Guzman et al.

Short summary

A new submicron-resolution spatial transcriptomics technique, Seq-Scope, has mapped the entire transcriptome of mouse soleus muscle, revealing detailed gene expression in muscle fibers, other cell types, and subcellular structures like neuromuscular junctions, both in health and after denervation.

AI-generated from the title and abstract; the full text is not read.

Key points

  • Seq-Scope technology provides submicron spatial resolution for whole-transcriptome analysis in muscle tissue.
  • A spatial transcriptomic atlas of the mouse soleus muscle was created under healthy and denervated conditions.
  • The study identified gene expression heterogeneity at single-cell and subcellular levels, including neuromuscular junctions and hybrid muscle fibers.
  • Findings reveal localized gene expression responses to denervation, mimicking aspects of muscle aging.

AI-generated from the title and abstract; the full text is not read.

Abstract

Skeletal muscle is essential for both movement and metabolic processes, characterized by a complex and ordered structure. Despite its importance, a detailed spatial map of gene expression within muscle tissue has been challenging to achieve due to the limitations of existing technologies, which struggle to provide high-resolution views. In this study, we leverage the Seq-Scope technique, an innovative method that allows for the observation of the entire transcriptome at an unprecedented submicron spatial resolution. By applying this technique to the mouse soleus muscle, we analyze and compare the gene expression profiles in both healthy conditions and following denervation, a process that mimics aspects of muscle aging. Our approach reveals detailed characteristics of muscle fibers, other cell types present within the muscle, and specific subcellular structures such as the postsynaptic nuclei at neuromuscular junctions, hybrid muscle fibers, and areas of localized expression of genes responsive to muscle injury, along with their histological context. The findings of this research significantly enhance our understanding of the diversity within the muscle cell transcriptome and its variation in response to denervation, a key factor in the decline of muscle function with age. This breakthrough in spatial transcriptomics not only deepens our knowledge of muscle biology but also sets the stage for the development of new therapeutic strategies aimed at mitigating the effects of aging on muscle health, thereby offering a more comprehensive insight into the mechanisms of muscle maintenance and degeneration in the context of aging and disease.

The authors' abstract, as published at the source. FEBS Journal, 2026 · DOI ↗

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Field: Molecular Biology

Molecular BiologyBiochemistry, Genetics and Molecular Biology