Single-cell RNA and ATAC sequencing reveals cell subsets characteristics in adipose-derived stem cells

The inherent heterogeneity of adipose-derived stem cells (ADSCs) complicates their characterization, as aggregated data obscure the nuanced states of individual cells and are skewed by dominant functional subpopulations affecting genetic and biological profiles. This heterogeneity presents a significant challenge for the effective deployment of ADSCs in clinical and research settings, highlighting the necessity for precise identification and isolation of specific subsets according to stringent criteria. Using single-cell RNA + ATAC multi-omics technology, we sequenced ADSCs derived from human adipose tissue through extraction, culture, and purification. This analysis identified three distinct subsets-proliferative, functional, and senescent-each exhibiting unique stemness properties. Notably, within the functional subset, cluster 6 emerged as a prime candidate for cellular engineering, showcasing robust stemness, high proliferative capacity, and low senescence. Our findings also reveal ADSCs' predisposition toward neuro-lineage differentiation, with their spatial distribution reflecting developmental trajectories and biological functions. In-depth analysis uncovered subset-specific genes with unique chromatin accessibility patterns, critical for targeted differentiation. Significantly, stemness markers BNC2 and HMGA2 were identified as indicators of non-senescent ADSCs. Through single-cell multi-omics sequencing, we have mapped a comprehensive cellular atlas of ADSCs, elucidating their transcriptional and chromatin profiles to unravel their complex heterogeneity. This atlas not only elucidates variations in composition, function, stemness, and developmental stages across subsets but also identifies essential biomarkers for ADSCs quality control, establishing a robust foundation for advancing ADSC-based therapeutic strategies.