{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yu Y"],"funding":["HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","NIDDK NIH HHS","MOST | National Key Research and Development Program of China","北京市科学技术委员会 | Natural Science Foundation of Beijing Municipality","Joslin Diabetes Center","MOST | National Natural Science Foundation of China"],"pagination":["e2316544121"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10945765"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["121(11)"],"pubmed_abstract":["Muscle regeneration is a complex process relying on precise teamwork between multiple cell types, including muscle stem cells (MuSCs) and fibroadipogenic progenitors (FAPs). FAPs are also the main source of intramuscular adipose tissue (IMAT). Muscles without FAPs exhibit decreased IMAT infiltration but also deficient muscle regeneration, indicating the importance of FAPs in the repair process. Here, we demonstrate the presence of bidirectional crosstalk between FAPs and MuSCs via their secretion of extracellular vesicles (EVs) containing distinct clusters of miRNAs that is crucial for normal muscle regeneration. Thus, after acute muscle injury, there is activation of FAPs leading to a transient rise in IMAT. These FAPs also release EVs enriched with a selected group of miRNAs, a number of which come from an imprinted region on chromosome 12. The most abundant of these is miR-127-3p, which targets the sphingosine-1-phosphate receptor <i>S1pr3</i> and activates myogenesis. Indeed, intramuscular injection of EVs from immortalized FAPs speeds regeneration of injured muscle. In late stages of muscle repair, in a feedback loop, MuSCs and their derived myoblasts/myotubes secrete EVs enriched in miR-206-3p and miR-27a/b-3p. The miRNAs repress FAP adipogenesis, allowing full muscle regeneration. Together, the reciprocal communication between FAPs and muscle cells via miRNAs in their secreted EVs plays a critical role in limiting IMAT infiltration while stimulating muscle regeneration, hence providing an important mechanism for skeletal muscle repair and homeostasis."],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Reciprocal communication between FAPs and muscle cells via distinct extracellular vesicle miRNAs in muscle regeneration."],"pmcid":["PMC10945765"],"funding_grant_id":["5222013","2R01DK082659","P30 DK036836","R01 DK082659","31970712","2P30DK036836","2021YFF1000603"],"pubmed_authors":["Lino M","Liu J","Meng Q","Kahn CR","Garcia Martin R","Wang G","Lan M","Liu C","Su Y","Brandao BB","Li L","Yu Y"],"additional_accession":[]},"is_claimable":false,"name":"Reciprocal communication between FAPs and muscle cells via distinct extracellular vesicle miRNAs in muscle regeneration.","description":"Muscle regeneration is a complex process relying on precise teamwork between multiple cell types, including muscle stem cells (MuSCs) and fibroadipogenic progenitors (FAPs). FAPs are also the main source of intramuscular adipose tissue (IMAT). Muscles without FAPs exhibit decreased IMAT infiltration but also deficient muscle regeneration, indicating the importance of FAPs in the repair process. Here, we demonstrate the presence of bidirectional crosstalk between FAPs and MuSCs via their secretion of extracellular vesicles (EVs) containing distinct clusters of miRNAs that is crucial for normal muscle regeneration. Thus, after acute muscle injury, there is activation of FAPs leading to a transient rise in IMAT. These FAPs also release EVs enriched with a selected group of miRNAs, a number of which come from an imprinted region on chromosome 12. The most abundant of these is miR-127-3p, which targets the sphingosine-1-phosphate receptor <i>S1pr3</i> and activates myogenesis. Indeed, intramuscular injection of EVs from immortalized FAPs speeds regeneration of injured muscle. In late stages of muscle repair, in a feedback loop, MuSCs and their derived myoblasts/myotubes secrete EVs enriched in miR-206-3p and miR-27a/b-3p. The miRNAs repress FAP adipogenesis, allowing full muscle regeneration. Together, the reciprocal communication between FAPs and muscle cells via miRNAs in their secreted EVs plays a critical role in limiting IMAT infiltration while stimulating muscle regeneration, hence providing an important mechanism for skeletal muscle repair and homeostasis.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2025-04-22T07:41:35.954Z","creation":"2025-04-05T22:14:01.281Z"},"accession":"S-EPMC10945765","cross_references":{"pubmed":["38442155"],"doi":["10.1073/pnas.2316544121"]}}