Origins, potency, and heterogeneity of skeletal muscle fibro-adipogenic progenitors—time for new definitions

Skeletal Muscle

Fabio M. V. Rossi¹  Marine Theret¹  Osvaldo Contreras² 

[1] Biomedical Research Centre, Department of Medical Genetics and School of Biomedical Engineering, University of British Columbia, V6T 1Z3, Vancouver, BC, Canada;Developmental and Stem Cell Biology Division, Victor Chang Cardiac Research Institute, 2010, Darlinghurst, NSW, Australia;St. Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney, 2052, Kensington, Australia;Departamento de Biología Celular y Molecular and Center for Aging and Regeneration (CARE-ChileUC), Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8331150, Santiago, Chile;

关键词: Mesenchymal stromal/stem cell;    Fibro/adipogenic progenitor;    Fibroblast;    Adipocyte;    Regeneration;    Single-cell RNAseq;   

DOI  :  10.1186/s13395-021-00265-6

来源: Springer

【 摘 要 】

Striated muscle is a highly plastic and regenerative organ that regulates body movement, temperature, and metabolism—all the functions needed for an individual’s health and well-being. The muscle connective tissue’s main components are the extracellular matrix and its resident stromal cells, which continuously reshape it in embryonic development, homeostasis, and regeneration. Fibro-adipogenic progenitors are enigmatic and transformative muscle-resident interstitial cells with mesenchymal stem/stromal cell properties. They act as cellular sentinels and physiological hubs for adult muscle homeostasis and regeneration by shaping the microenvironment by secreting a complex cocktail of extracellular matrix components, diffusible cytokines, ligands, and immune-modulatory factors. Fibro-adipogenic progenitors are the lineage precursors of specialized cells, including activated fibroblasts, adipocytes, and osteogenic cells after injury. Here, we discuss current research gaps, potential druggable developments, and outstanding questions about fibro-adipogenic progenitor origins, potency, and heterogeneity. Finally, we took advantage of recent advances in single-cell technologies combined with lineage tracing to unify the diversity of stromal fibro-adipogenic progenitors. Thus, this compelling review provides new cellular and molecular insights in comprehending the origins, definitions, markers, fate, and plasticity of murine and human fibro-adipogenic progenitors in muscle development, homeostasis, regeneration, and repair.

【 授权许可】

CC BY