 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Apr 19, 2021 |
| Title |
Single-cell Transcriptomics Identifies Gene Expression Networks Driving Differentiation and Tumorigenesis in the Human Fallopian Tube |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The human fallopian tube harbors the cell-of-origin for the majority of high-grade serous ‘ovarian’ cancers (HGSCs), but its cellular composition, particularly of the epithelial component, is poorly characterized. We performed single-cell transcriptomic profiling in 12 primary fallopian specimens from 8 patients, analyzing around 53,000 individual cells to map the major immune, fibroblastic and epithelial cell types present in this organ. We identified 10 epithelial sub-populations, characterized by diverse transcriptional programs including SOX17 (enriched in secretory epithelial cells), TTF3 and RFX3 (enriched in ciliated cells) and NR2F2 (enriched in early, partially differentiated secretory cells). Based on transcriptional signatures, we reconstructed a trajectory whereby secretory cells differentiate into ciliated cells via a RUNX3high intermediate. Computational deconvolution of the cellular composition of advanced HGSCs based on epithelial subset signatures identified the ‘early secretory’ population as a likely precursor state for the majority of HGSCs. The signature of this rare population of cells comprised both epithelial (EPCAM, KRT) and mesenchymal (THY1, ACTA2) features, and was enriched in mesenchymal-type HGSCs (P = 6.7 x 10-27), a group known to have particularly poor prognoses. This cellular and molecular compendium of the human fallopian tube in cancer-free women is expected to advance our understanding of the earliest stages of fallopian epithelial neoplasia.
PAX8, SOX17, MECOM, and WT1 are critical genes in high-grade ovarian cancer tumorigenesis. However, the target genes of these factors in a normal to tumor context is unknown. Depletion of these factors in fallopian tube secretory epithelial and high-grade serous ovarian cancer cells revealed transcription factor and cell-type dependent differential expression patterns.
|
| |
|
| Overall design |
siRNA knock-down of two non-targeting controls, PAX8, SOX17, DUAL(PAX8/SOX17), MECOM,and WT1 in cell lines followed by bulk RNA sequencing. This series includes re-analysis of all samples in GSE150443.
|
| |
|
| Contributor(s) |
Dinh HQ, Lin X, Abbasi F, Nameki R, Haro M, Olingy CE, Chang H, Hernandez L, Gayther S, Wright KN, Aspuria P, Y.Karlan B, Corona RI, Li A, Rimel BJ, Siedhoff M, Medeiros F, Lawrenson K |
| Citation(s) |
33852846, 37090516 |
| Submission date |
May 27, 2020 |
| Last update date |
May 12, 2023 |
| Contact name |
Robbin Nameki |
| E-mail(s) |
Robbin.Nameki@cshs.org, Robbinnameki4@gmail.com
|
| Organization name |
Cedars-Sinai Medical Center
|
| Department |
Obstetrics and Gynecology
|
| Lab |
Lawrenson
|
| Street address |
8700 Beverly Blvd
|
| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90048 |
| Country |
USA |
| |
|
| Platforms (1) |
|
| Samples (28)
|
|
| Relations |
| BioProject |
PRJNA635428 |
| SRA |
SRP264994 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE151316_siRNAKD_OVCAR4_FT282.sorted.htseq-count.txt.gz |
1.3 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...