Cytokines produced by muscle stem cells in muscle regeneration

Cell-cell communication during muscle regeneration is mediated largely by secreted signaling molecules, collectively referred to as cytokines. Upon acute muscle injury, residential and infiltrating immune cells at the injury site clear tissue debris and regulate muscle stem cell (MuSC) function to promote new myofiber formation. The importance of immune cell-derived cytokines in muscle regeneration has been established. However, it is now well accepted that other types of cells in the regenerating muscle, including MuSCs, also secrete cytokines, the functions of which are far less well understood. Our interrogation of publicly available single-cell RNA sequencing data has revealed widespread cytokine expression by MuSCs during injury-induced regeneration. Our productive investigation of muscle cell-derived cytokines in myogenic differentiation in recent years has now transitioned to focusing on in vivo roles of MuSC-derived cytokines in autocrine signaling as well as communication to other types of cells in the regenerating muscle niche.

Y. Ge, R. J. Waldemer, R. Nalluri, P. D. Nuzzi, and J. Chen, (2013) RNAi screen reveals potentially novel roles of cytokines in myoblast differentiation, PLoS One, 8, e68068. Link to article

Y. Ge, R. J. Waldemer, R. Nalluri, P. D. Nuzzi, and J. Chen, (2013) Flt3L is a novel regulator of skeletal myogenesis, J. Cell Sci., 126, 3370-9. Link to article

R. J. Waldemer-Streyer and J. Chen, (2015) Myocyte-derived Tnfsf14 is a survival factor necessary for myoblast differentiation and skeletal muscle regeneration, Cell Death & Disease, 6, e2026. Link to article

R. J. Waldemer-Streyer, A. Reyes-Ordoñez, D. Kim, R. Zhang, and J. Chen, (2017) Cxcl14 depletion accelerates skeletal myogenesis by promoting cell cycle withdrawal, NPJ Regenerative Medicine, 2, 16017. Link to article

D. Kim, N. Singh, R. J. Waldemer-Streyer, M.S. Yoon, and J. Chen, (2020) Muscle-derived TRAIL negatively regulates myogenic differentiation. Exp. Cell Res. 394, 112165. Link to article

R. J. Waldemer-Streyer, D. Kim, and J. Chen, (2022) Muscle cell-derived cytokines in skeletal muscle regeneration (state-of-the-art review). FEBS J. 289, 6463. [Ranked top 10% of the most-read papers in the journal within one year of publication.] Link to article

A. Boss-Kennedy, Kim, D, P. Barai, C. Maldonado, A. Reyes-Ordoñez, and J. Chen, (2024) Muscle cell-derived Ccl8 is a negative regulator of skeletal muscle regeneration. FASEB J. 38, e23841. Link to article

P. Barai and J. Chen, (2024) Cytokine expression and cytokine-mediated cell-cell communication during skeletal muscle regeneration revealed by integrative analysis of single-cell RNA sequencing data. J. Cell Communication and Signaling, 18, e12055. Link to article

The Chen Lab
Email: jiechen@illinois.edu