ИСТИНА

The heterogeneity of adipose tissue-derived mesenchymal stem/stromal cells (MSCs) has long been a topic of interest. In this study, we performed single-cell RNA sequencing (scRNA-seq) on MSCs isolated from human subcutaneous white adipose tissue (WAT) and cultured under both control conditions and adipogenic induction for 4 days. Our analysis identified a distinct subpopulation of T-cadherin-expressing cells that co-expressed dipeptidyl peptidase-4 (DPP4), a known marker of interstitial progenitors in adipose tissue and other stemness-associated genes (Notch1, Notch3, Wnt family members, N-cadherin, Neuropilin 2, IGFBP4, key MSC markers (CD90, PDGFR), LDLR, adipogenesis regulatory factor and etc.). Upon adipogenic induction, T-cadherin expression declined overall; however, a subset of cells retained high T-cadherin levels and stemness-related genes, such as NANOG, SPN, SOX2, PRMT8. Pseudotemporal trajectory analysis of scRNA-seq data revealed that T-cadherin-expressing cells represented a discrete stem-like subpopulation rather than participating in adipogenic differentiation. Functional assays using lentiviral transduction demonstrated that T-cadherin overexpression significantly reduced MSC proliferation rates. Long-term live-cell imaging over 10 days further revealed a substantial reduction in adipogenic differentiation capacity among T-cadherin-overexpressing MSCs. Interestingly, T-cadherin-expressing cells also suppressed adipogenic differentiation in the surrounding cells, likely through exosome-mediated signaling. Consistently, scRNA-seq analysis revealed an upregulation of exosome markers (CD9, CD63, CAV1) in T-cadherin-expressing cells, implicating their potential role in modulating MSC differentiation. Taken together, our findings identify a distinct T-cadherin-expressing MSC subpopulation characterized by stem-like properties and a regulatory role in adipogenic differentiation, providing new insights into the mechanisms governing adipose tissue homeostasis.