Fig. 1: The evolution of transcriptomic resolution reveals MuSC heterogeneity and niche context during aging.

This timeline illustrates three eras of technological advancement (bottom arrow) that have progressively increased the resolution of research on aged muscle stem cells (MuSCs). ERA 1 (left): Early bulk profiling methods (microarray, bulk RNA-seq) averaged transcriptional signals across heterogeneous populations. ERA 2 (middle): The advent of single-cell resolution (scRNA-seq, snRNA-seq) enabled dissection of dissociated MuSCs. Key insight: these advances revealed cellular heterogeneity within the MuSC pool, identified distinct subpopulations, and enabled reconstruction of dynamic differentiation trajectories. ERA 3 (right): Emerging spatial technologies preserve native tissue architecture, while multi-omic integration captures diverse molecular layers. Key insight: by integrating spatial context with multiple omics layers (e.g., genomics, transcriptomics, proteomics, epigenomics, and metabolomics), these approaches enable a deeper understanding of MuSC–niche interactions and regulatory networks in situ.