Cell type specific differences in transcriptome profiles of adipose derived stem cells and vaginal fibroblasts in patients with pelvic organ prolapse.

The purpose of this study was to understand the molecular phenotypes of adipose-derived stem cells (ASCs) and vaginal fibroblasts (VFBs) and whether pelvic organ prolapse (POP) affects their biological properties. We performed RNA sequencing of paired ASCs and VFBs from six patients with POP and six controls (CTRL). The transcriptomes of POP and CTRL in either ASCs or VFBs were compared (DESeq2, false discovery rate (FDR) < 0.05) to identify differentially expressed genes (DEG). The transcriptomes of VFBs were compared between POP and CTRL (non-adjusted p < 0.01) followed by Ingenuity Pathway Analysis on DEG considering that pathways with FDR < 0.05 might be pathogenic. Lastly, we performed a pairwise comparison after combining the gene expression data of POP and CTRL for ASCs and VFBs to identify cell type specific DEG and analyzed the functional associations among them (STRING platform). We found no DEG between POP and CTRL in ASCs and VFBs. Less stringent statistical analysis of VFBs transcriptome showed 23 genes with higher and 29 genes with lower expression in POP compared to CTRL. Among the latter were five genes involved in the synaptogenesis pathway found to be significant. We were only able to validate POP related differences for very low density receptor (VLDLR). We found 508 DEG with 4-fold difference between ASCs and VFBs (both POP and CTRL groups combined for each cell type) which formed cell type distinct functional networks including Homeobox transcription factors, extracellular matrix (ECM) related proteins, and growth factors. In summary, this study showed that cell-specific RNA populations are intrinsically more characteristic than the disease peculiarities. VLDLR may play a role in POP pathogenesis.