A transcriptome atlas of leg muscles from healthy human volunteers reveals molecular and cellular signatures associated with muscle location
- Leiden University Medical Center, Netherlands
- Erasmus MC, Netherlands
- Medisch Centrum Haaglanden, Netherlands
- Radboud University Nijmegen Medical Centre, Netherlands
Abstract
Skeletal muscles support the stability and mobility of the skeleton but differ in biomechanical properties and physiological functions. The intrinsic factors that regulate muscle-specific characteristics are poorly understood. To study these, we constructed a large atlas of RNA-seq profiles from six leg muscles and two locations from one muscle, using biopsies from 20 healthy young males. We identified differential expression patterns and cellular composition across the seven tissues using three bioinformatics approaches confirmed by large-scale newly developed quantitative immune-histology procedures. With all three procedures, the muscle samples clustered into three groups congruent with their anatomical location. Concomitant with genes marking oxidative metabolism, genes marking fast- or slow-twitch myofibers differed between the three groups. The groups of muscles with higher expression of slow-twitch genes were enriched in endothelial cells and showed higher capillary content. In addition, expression profiles of Homeobox (HOX) transcription factors differed between the three groups and were confirmed by spatial RNA hybridization. We created an open-source graphical interface to explore and visualize the leg muscle atlas (https://tabbassidaloii.shinyapps.io/muscleAtlasShinyApp/). Our study reveals the molecular specialization of human leg muscles, and provides a novel resource to study muscle-specific molecular features, which could be linked with (patho)physiological processes.
Data availability
The raw data is publicly available at the European Genome Archive (Dataset ID: EGAS00001005904, https://ega-archive.org/). The muscle transcriptomics atlas is available for exploration through a graphical user interface (https://tabbassidaloii.shinyapps.io/muscleAtlasShinyApp/).
Article and author information
Author details
Funding
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (917.164.90)
- Hermien E Kan
Association France Myopathies (22506)
- Vered Raz
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Christopher L-H Huang, University of Cambridge, United Kingdom
Ethics
Human subjects: The study was approved by the local Medical Ethical Review Board of The Hague Zuid-West and the Erasmus Medical Centre and conducted in accordance with the ethical standards stated in the 1964 Declaration of Helsinki and its later amendments (ABR number: NL54081.098.16). All subjects provided written informed consent prior to participation.
Version history
- Received: May 23, 2022
- Preprint posted: June 1, 2022 (view preprint)
- Accepted: February 3, 2023
- Accepted Manuscript published: February 6, 2023 (version 1)
- Version of Record published: March 6, 2023 (version 2)
- Version of Record updated: March 13, 2023 (version 3)
Copyright
© 2023, Abbassi-Daloii et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A transcriptome atlas of leg muscles from healthy human volunteers reveals molecular and cellular signatures associated with muscle location
eLife 12:e80500.
https://doi.org/10.7554/eLife.80500
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