Distinct myofibre domains of the human myotendinous junction revealed by single-nucleus RNA sequencing

Anders Karlsen, Ching-Yan Chloé Yeung, Peter Schjerling, Linda Denz, Christian Hoegsbjerg, Jens R Jakobsen, Michael R Krogsgaard, Manuel Koch, Stefano Schiaffino, Michael Kjaer, Abigail L Mackey

Abstract

The myotendinous junction (MTJ) is a specialized domain of the multinucleated myofibre that is faced with the challenge of maintaining robust cell-matrix contact with the tendon under high mechanical stress and strain. Here, we profiled 24,124 nuclei in semitendinosus muscle-tendon samples from three healthy males by using single-nucleus RNA sequencing (snRNA-seq), alongside spatial transcriptomics, to gain insight into the genes characterizing this specialization in humans. We identified a cluster of MTJ myonuclei represented by 47 enriched transcripts, of which the presence of ABI3BP, ABLIM1, ADAMTSL1, BICD1, CPM, FHOD3, FRAS1 and FREM2 was confirmed at the MTJ at the protein level in immunofluorescence assays. Four distinct subclusters of MTJ myonuclei were apparent, comprising two COL22A1-expressing subclusters and two subclusters lacking COL22A1 expression but with differing fibre type profiles characterized by expression of either MYH7 or MYH1 and/or MYH2. Our findings reveal distinct myonuclei profiles of the human MTJ, which represents a weak link in the musculoskeletal system that is selectively affected in pathological conditions ranging from muscle strains to muscular dystrophies.

Original languageEnglish
Article numberjcs260913
JournalJournal of Cell Science
Volume136
Issue number8
ISSN0021-9533
DOIs
Publication statusPublished - 15 Apr 2023

Keywords

  • Male
  • Humans
  • Myotendinous Junction
  • Tendons/physiology
  • Cell Nucleus/metabolism
  • Muscle, Skeletal/metabolism
  • Microfilament Proteins/metabolism
  • LIM Domain Proteins/metabolism
  • Cytoskeletal Proteins/metabolism
  • Adaptor Proteins, Signal Transducing/metabolism
  • Formins/metabolism

Fingerprint

Dive into the research topics of 'Distinct myofibre domains of the human myotendinous junction revealed by single-nucleus RNA sequencing'. Together they form a unique fingerprint.

Cite this