Therapeutic potential of umbilical cord-derived mesenchymal stem cells in ameliorating ovarian aging: Insights from single-cell analysis

Figure 6 Umbilical cord-derived mesenchymal stem cell transplantation induces cell-type-specific transcriptomic reprogramming and upregulates the anti-aging gene Klotho. A: Volcano plots showing the numbers of upregulated and downregulated differentially expressed genes (DEGs) in major ovarian cell types between the umbilical cord-derived mesenchymal stem cell (UCMSC) transplantation and aged control groups. Granulosa cells (GCs) and stromal cells (SCs) exhibited the most pronounced changes; B: Functional enrichment analysis of upregulated DEGs; C: Functional enrichment analysis of downregulated DEGs; D: Heatmap showing the differential expression levels of key anti-aging genes from the GenAge database across cell types. Klotho was significantly upregulated in granulosa cells; E: Senescence scores calculated for each cell type based on the GenAge database gene set. UCMSC transplantation significantly reduced senescence scores in granulosa cells and epithelial cells; F: Klotho expression by cell type and sample; G: Proportion of Klotho-positive cells by cell type and sample; H: Representative immunohistochemical images of KLOTHO protein in ovarian sections; I: Quantification of KLOTHO protein expression in ovarian sections. UCMSC transplantation markedly enhanced KLOTHO expression. ^aP < 0.05, ^bP < 0.01, ^cP < 0.001, ^dP < 0.0001. GC: Granulosa cell; SC: Stromal cell; TC: Theca cell; EndoC: Endothelial cell; EpiC: Epithelial cell; IC: Immune cell; A-CON: Aged control; A-MSC: Umbilical cord-derived mesenchymal stem cell transplantation.