Defining a Muscle Stem Cell matrisome signature: from transcriptome data to extracellular matrix niche topology

Although intensively investigated, the regulation of skeletal muscle stem cells (MuSCs) by their niche remains an open question. The extracellular matrix (ECM) components of the niche represent a dynamic microenvironment that undoubtedly participates in MuSCs behavior. We used bioinformatics analysis of transcriptomic data to define the matrisome profile of skeletal muscle resident cells, comprising genes encoding ECM and ECM-associated proteins. We identified quiescent MuSCs as key ECM producers of the niche, notably through the expression of specific basement membrane genes as Col19a1 and Lama3 and regulators of ECM assembly, Thsd4 and Aebp1 . Unexpectedly, quiescent MuSCs also expressed matrisome neurogenesis-related genes. Immunofluorescence staining of selected ECM components showed their organization in isolated murine myofiber bundles. Upon activation, MuSCs strikingly downregulated the niche-related ECM genes and instead expressed genes involved in basement membrane disruption and matrisome genes linked to cell motility. This study identified distinct matrisome signatures of quiescent and activated MuSCs that are consistent with their function in homeostasis and repair of damaged skeletal muscle.