# Single-Cell Sequencing Reveals the Crosstalk Between MuSCs and FAPs in Ruminant Skeletal Muscle Development

## TL;DR

This study uses single-cell sequencing to explore how muscle and fat-related cells interact during goat muscle development from birth to old age.

## Contribution

The first single-cell RNA sequencing atlas of skeletal muscle in ruminants, revealing crosstalk between MuSCs and FAPs across 14 developmental stages.

## Key findings

- A unique MuSCs_ACT1_high subpopulation was identified in early embryogenesis.
- FAPs_MDFI_high subpopulation showed potential to differentiate into adipogenic and fibrogenic lineages.
- DLK1-NOTCH3 signaling was found to maintain MuSC quiescence in early embryonic FAPs.

## Abstract

Skeletal muscle orchestrates a remarkable journey from embryonic formation to age-related decline, yet its cellular intricacies in goats remain largely uncharted. We present the first single-cell RNA sequencing (scRNA-seq) atlas of the longissimus dorsi muscle from goats, profiling 120,944 cells across 14 developmental stages from embryonic day 30 (E30) to 11 years postnatal (Y11). We focused on skeletal muscle satellite cells (MuSCs) and fibro-adipogenic progenitors (FAPs), identifying a unique MuSCs_ACT1_high subpopulation in early embryogenesis and a senescence-associated MuSCs_CDKN1A_high subpopulation in later developmental stages. In FAPs, we characterized the early-stage FAPs_MDFI_high subpopulation with differentiation potential, which further exhibited the capacity to commit to both adipogenic and fibrogenic lineages. Transcription factor analysis revealed strikingly similar regulatory profiles between MuSCs and FAPs, suggesting that these two cell types are governed by shared signaling pathways during development. Cell–cell interaction analysis demonstrated that the DLK1-NOTCH3 ligand-receptor pair plays a critical role in enabling early embryonic FAPs to maintain the quiescent state of MuSCs. This dynamic single-cell transcriptomic atlas, spanning 14 developmental stages of skeletal muscle in ruminants for the first time, provides a valuable theoretical foundation for further elucidating the differentiation of skeletal muscle satellite cells and fibro-adipogenic progenitors in ruminants.