Spatial multi-omics in whole skeletal muscle reveals complex tissue architecture

Communications Biology, vol. 7, pp. 1272

Abstract

Myofibers are large multinucleated cells that have long thought to have a rather simple organization. Single-nucleus transcriptomics, spatial transcriptomics and spatial metabolomics analysis have revealed distinct transcription profiles in myonuclei related to myofiber type. However, the use of local tissue collection or dissociation methods have obscured the spatial organization. To elucidate the full tissue architecture, we combine two spatial omics, RNA tomography and mass spectrometry imaging. This enables us to map the spatial transcriptomic, metabolomic and lipidomic organization of the whole murine tibialis anterior muscle. Our findings on heterogeneity in fiber type proportions are validated with multiplexed immunofluorescence staining in tibialis anterior, extensor digitorum longus and soleus. Our results demonstrate unexpectedly strong regionalization of gene expression, metabolic differences and variable myofiber type proportion along the proximal-distal axis. These new insights in whole-tissue level organization reconcile sometimes conflicting results coming from previous studies relying on local sampling methods. Multi-dimensional analysis of gene expression, myofiber types and metabolic activity in whole skeletal muscle reveals specific regionalization of gene expression and metabolites related to the glycolytic and oxidative potential of myofibers

Authors 9

1. Clara Martínez Mir Aachen Department of Anatomy and Embryology

   Leiden University Medical Center · Novo Nordisk Foundation Center for Stem Cell Medicine

   Affiliation as printed

   Department of Anatomy and Embryology, Leiden University Medical Center, 2333, Leiden, The Netherlands

   The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden Node, Leiden, The Netherlands

2. Paola Pisterzi Aachen Department of Anatomy and Embryology

   Leiden University Medical Center · Novo Nordisk Foundation Center for Stem Cell Medicine

   Affiliation as printed

   Department of Anatomy and Embryology, Leiden University Medical Center, 2333, Leiden, The Netherlands

   The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden Node, Leiden, The Netherlands

3. Isabel de Poorter Aachen Department of Anatomy and Embryology

   Leiden University Medical Center · Novo Nordisk Foundation Center for Stem Cell Medicine

   Affiliation as printed

   Department of Anatomy and Embryology, Leiden University Medical Center, 2333, Leiden, The Netherlands

   The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden Node, Leiden, The Netherlands

4. Maria Rilou Aachen Department of Anatomy and Embryology

   Leiden University Medical Center · Novo Nordisk Foundation Center for Stem Cell Medicine

   Affiliation as printed

   Department of Anatomy and Embryology, Leiden University Medical Center, 2333, Leiden, The Netherlands

   The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden Node, Leiden, The Netherlands

5. Melissa van Kranenburg Aachen Department of Anatomy and Embryology

   Leiden University Medical Center · Novo Nordisk Foundation Center for Stem Cell Medicine

   Affiliation as printed

   Department of Anatomy and Embryology, Leiden University Medical Center, 2333, Leiden, The Netherlands

   The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden Node, Leiden, The Netherlands

6. Bram Heijs Aachen Center of Proteomics and Metabolomics

   Leiden University Medical Center · Novo Nordisk Foundation Center for Stem Cell Medicine

   Affiliation as printed

   Bruker Daltonics GmbH & Co. KG, Bremen, Germany

   Center of Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands

   The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden Node, Leiden, The Netherlands

7. Anna Alemany Aachen Department of Anatomy and Embryology

   Leiden University Medical Center · Novo Nordisk Foundation Center for Stem Cell Medicine

   Affiliation as printed

   Department of Anatomy and Embryology, Leiden University Medical Center, 2333, Leiden, The Netherlands

   The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden Node, Leiden, The Netherlands

8. Fanny Sage corresponding Aachen Department of Anatomy and Embryology

   Leiden University Medical Center · Novo Nordisk Foundation Center for Stem Cell Medicine

   Affiliation as printed

   Department of Anatomy and Embryology, Leiden University Medical Center, 2333, Leiden, The Netherlands. f.g.sage@lumc.nl

   The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden Node, Leiden, The Netherlands. f.g.sage@lumc.nl

9. Niels Geijsen corresponding Aachen Department of Anatomy and Embryology

   Leiden University Medical Center · Novo Nordisk Foundation Center for Stem Cell Medicine

   Affiliation as printed

   Department of Anatomy and Embryology, Leiden University Medical Center, 2333, Leiden, The Netherlands. n.geijsen@lumc.nl

   The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden Node, Leiden, The Netherlands. n.geijsen@lumc.nl