Modeling the <i>ACVR1</i><sup><i>R206H</i></sup> mutation in human skeletal muscle stem cells.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34755602.
- Also identified by DOI 10.7554/eLife.66107 and PMC identifier 8691832.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Abnormalities in skeletal muscle repair can lead to poor function and complications such as scarring or heterotopic ossification (HO). Here, we use fibrodysplasia ossificans progressiva (FOP), a disease of progressive HO caused by <i>ACVR1</i><sup><i>R206H</i></sup> (Activin receptor type-1 receptor) mutation, to elucidate how ACVR1 affects skeletal muscle repair. Rare and unique primary FOP human muscle stem cells (Hu-MuSCs) isolated from cadaveric skeletal muscle demonstrated increased extracellular matric (ECM) marker expression, showed skeletal muscle-specific impaired engraftment and regeneration ability. Human induced pluripotent stem cell (iPSC)-derived muscle stem/progenitor cells (iMPCs) single-cell transcriptome analyses from FOP also revealed unusually increased ECM and osteogenic marker expression compared to control iMPCs. These results show that iMPCs can recapitulate many aspects of Hu-MuSCs for detailed in vitro study; that ACVR1 is a key regulator of Hu-MuSC function and skeletal muscle repair; and that ACVR1 activation in iMPCs or Hu-MuSCs may contribute to HO by changing the local tissue environment.
Medical subject headings
- Activin Receptors, Type I
- Induced Pluripotent Stem Cells
- Muscle Fibers, Skeletal
- Mutation
- Myositis Ossificans