A transcriptome atlas of leg muscles from healthy human volunteers reveals molecular and cellular signatures associated with muscle location

  1. Tooba Abbassi-Daloii
  2. Salma el Abdellaoui
  3. Lenard M Voortman
  4. Thom TJ Veeger
  5. Davy Cats
  6. Hailiang Mei
  7. Duncan E Meuffels
  8. Ewoud van Arkel
  9. Peter AC 't Hoen  Is a corresponding author
  10. Hermien E Kan  Is a corresponding author
  11. Vered Raz  Is a corresponding author
  1. Leiden University Medical Center, Netherlands
  2. Erasmus MC, Netherlands
  3. Medisch Centrum Haaglanden, Netherlands
  4. 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

  1. Tooba Abbassi-Daloii

    Leiden University Medical Center, Leiden, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  2. Salma el Abdellaoui

    Leiden University Medical Center, Leiden, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  3. Lenard M Voortman

    Leiden University Medical Center, Leiden, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9794-067X
  4. Thom TJ Veeger

    Leiden University Medical Center, Leiden, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  5. Davy Cats

    Leiden University Medical Center, Leiden, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  6. Hailiang Mei

    Leiden University Medical Center, Leiden, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  7. Duncan E Meuffels

    Erasmus MC, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5372-6003
  8. Ewoud van Arkel

    Department of Orthopedics, Medisch Centrum Haaglanden, Den haag, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  9. Peter AC 't Hoen

    Radboud University Nijmegen Medical Centre, Radboud, Netherlands
    For correspondence
    peter-bram.thoen@radboudumc.nl
    Competing interests
    The authors declare that no competing interests exist.
  10. Hermien E Kan

    Leiden University Medical Center, Leiden, Netherlands
    For correspondence
    H.E.Kan@lumc.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5772-7177
  11. Vered Raz

    Leiden University Medical Center, Leiden, Netherlands
    For correspondence
    v.raz@lumc.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3152-1952

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

  1. 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

  1. Received: May 23, 2022
  2. Preprint posted: June 1, 2022 (view preprint)
  3. Accepted: February 3, 2023
  4. Accepted Manuscript published: February 6, 2023 (version 1)
  5. Version of Record published: March 6, 2023 (version 2)
  6. 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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  1. Tooba Abbassi-Daloii
  2. Salma el Abdellaoui
  3. Lenard M Voortman
  4. Thom TJ Veeger
  5. Davy Cats
  6. Hailiang Mei
  7. Duncan E Meuffels
  8. Ewoud van Arkel
  9. Peter AC 't Hoen
  10. Hermien E Kan
  11. Vered Raz
(2023)
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

Share this article

https://doi.org/10.7554/eLife.80500

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