SRA

Many high-grade serous carcinomas (HGSCs) likely originate in the distal region of the Fallopian tube's epithelium (TE) before metastasizing to the ovary. Unfortunately, molecular mechanisms promoting malignancy in the distal TE are obfuscated, largely due to limited primary human TE gene expression data. Here we report an in depth bioinformatic characterization of 34 primary TE mRNA-seq samples. These samples were prepared from proximal and distal TE regions of 12 normal Fallopian tubes. Samples were segregated based on their aldehyde dehydrogenase (ALDH) activity. Distal cells form organoids with higher frequency and larger size during serial organoid formation assays when comparted to proximal cells. Consistent with enrichment for stem/progenitor cells, ALDH+ cells have greater WNT signaling. Comparative evaluation of proximal and distal TE cell population's shows heightened inflammatory signaling in distal differentiated (ALDH-) TE. Furthermore, comparisons of proximal and distal TE cell populations finds that the distal ALDH+ TE cells exhibit pronounced expression of gene sets characteristic of HGSC sub-types. Overall, our study indicates increased organoid forming capacity, WNT/inflammatory signaling, and HGSC signatures underlie differences between distal and proximal regions of the human TE. These findings provide the basis for further mechanistic studies of distal TE susceptibility to the malignant transformation. Overall design: Primary human epithelial cells from proximal and distal Fallopian tube fragments were isolated by FACS before being used to construct 3' mRNA-seq libraries with UMIs according to Lexogen's QuantSeq protocol. ALDH activity was used to enrich for stem or differentiated cells from each proximal or distal Fallopian tube fragment. In total 7 proximal EpCAM+/ALDH-, 9 proximal EpCAM+/ALDH+, 10 distal EpCAM+/ALDH-, 8 distal EpCAM+/ALDH+ samples were collected and sequenced. DESeq2 was used to identify differentially expressed genes between stem and differentiated cell enriched populations from the proximal and distal regions of the Fallopian tube.