Single-cell analysis reveals conserved regulons shaping muscle stem cell behavior during development and aging in mammals

Abstract

<p>Muscle stem cells (MuSCs) play a pivotal role in skeletal muscle development, regeneration, and maintenance. Previous studies have extensively investigated the transcriptional changes in MuSCs during various developmental stages in mammals using single-cell RNA sequencing. However, a gap remains in cross-species integrative research examining the factors influencing MuSC activity during development and aging. To address this gap, we constructed a conserved single-cell landscape of MuSCs in mammals, encompassing their developmental and aging stages. Our findings unveil a conserved developmental coordinate between human and mouse MuSCs, shedding light on their shared biology. The single-cell coordinated gene association in pattern sets (scCoGAPS) algorithm and dynamic time warping algorithm were used to investigate the temporal dynamics of skeletal muscle regeneration related gene patterns. Additionally, we scrutinized the conservation of regulons, delineating groups of genes under the influence of common transcription factors, particularly emphasizing the identification of pivotal factors governing MuSC behavior during aging. Notably, we identified USF2, a conserved regulon, as a key regulator influencing muscle cell myogenesis and aging. This research provides critical insights into the conserved aspects that influence MuSC behavior and highlights the significance of USF2 in MuSC regulation. By unraveling the intricate mechanisms underlying MuSC development and aging, our study opens avenues for advancements in regenerative medicine and muscle-related therapeutics.</p>