The chemokine receptor CXCR4 regulates satellite cell activation, early expansion, and self-renewal, in response to skeletal muscle injury

Ahmed S. Shams, Robert W Arpke, Micah D. Gearhart, Johannes Weiblen, Ben Mai, David Oyler, Darko Bosnakovski, Omayma M. Mahmoud, Gamal M. Hassan, Michael Kyba

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Acute skeletal muscle injury is followed by satellite cell activation, proliferation, and differentiation to replace damaged fibers with newly regenerated muscle fibers, processes that involve satellite cell interactions with various niche signals. Here we show that satellite cell specific deletion of the chemokine receptor CXCR4, followed by suppression of recombination escapers, leads to defects in regeneration and satellite cell pool repopulation in both the transplantation and in situ injury contexts. Mechanistically, we show that endothelial cells and FAPs express the gene for the ligand, SDF1α, and that CXCR4 is principally required for proper activation and for transit through the first cell division, and to a lesser extent the later cell divisions. In the absence of CXCR4, gene expression in quiescent satellite cells is not severely disrupted, but in activated satellite cells a subset of genes normally induced by activation fail to upregulate normally. These data demonstrate that CXCR4 signaling is essential to normal early activation, proliferation, and self-renewal of satellite cells.

Original languageEnglish (US)
Article number949532
JournalFrontiers in Cell and Developmental Biology
Volume10
DOIs
StatePublished - Sep 22 2022

Bibliographical note

Funding Information:
This work was supported by a grant from the National Institute on Aging (R01 AG062899) and by the Egyptian Cultural and Education Bureau Joint Supervision Program (JS 3732).

Funding Information:
The National Natural Science Foundation (No. 81873786) supported this work.

Publisher Copyright:
Copyright © 2022 Shams, Arpke, Gearhart, Weiblen, Mai, Oyler, Bosnakovski, Mahmoud, Hassan and Kyba.

Keywords

  • CXCR4
  • activation
  • regeneration
  • satellite cells
  • skeletal muscle

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