Single cell RNA-seq data for mouse fallopian tube and ovary
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE194274 | GEO | 2022/12/27
REPOSITORIES: GEO
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Project description:The cell-of-origin of high grade serous ovarian carcinoma (HGSOC) remains controversial, with fallopian tube epithelium (FTE) and ovarian surface epithelium (OSE) both considered candidates. Here, by using genetically engineered mouse models and organoids, we assessed the tumor-forming properties of FTE and OSE harboring the same oncogenic abnormalities. Combined RB family inactivation and Tp53 mutation in Pax8+ FTE caused Serous Tubal Intraepithelial Carcinoma (STIC), which metastasized rapidly to the ovarian surface. These events were recapitulated by orthotopic injection of mutant FTE organoids. Engineering the same genetic lesions into Lgr5+ OSE or OSE-derived organoids also caused metastatic HGSOC, although with longer latency and lower penetrance. FTE- and OSE-derived tumors had distinct transcriptomes, and comparative transcriptomics and genomics suggest that human HGSOC arises from both cell types. Finally, FTE- and OSE-derived organoids exhibited differential chemosensitivity. Our results comport with a dualistic origin for HGSOC and suggest that the cell-of-origin might influence therapeutic response.
2019-10-21 | GSE125016 | GEO
Project description:We analyzed primary cells derived from patients with ovarian cancer. We compared OSE, FTE and EOC and we use quantitative propeomics followed by WB, IHC, TMA for validation of our findings. We also analyzed the phosphoproteome of OVCAR3.
2017-04-03 | PXD003531 | Pride
Project description:The cell and tissue of origin of high grade serous ovarian cancer (HGSC) is controversial. While the disease was traditionally assumed to arise from the ovarian surface epithelium (OSE), recent work supports an alternative model implicating the fallopian tube fimbriae epithelium (FTE). We used comparative DNA methylome analyses as a means to test these two competing models, hypothesizing that the HGSC methylome should more closely resemble its tissue of origin. Using two separate analysis methods, analysis within distinct genomic contexts, and validation studies using large-scale publically available HGSC methylome data, we consistently observed that the DNA methylome of HGSC more closely resembles FTE than OSE. These data support the FTE origin model, and suggest DNA methylome analysis as a useful approach to examine cell/tissue lineage origin in cancer. HGSC is the most common and lethal form of epithelial ovarian cancer (EOC). Two distinct tissues have been hypothesized as the tissue of origin of HGSC: OSE and FTE. We hypothesized that the DNA methylome of HGSC would more closely resemble the methylome of its tissue of origin. To test this, we profiled HGSC (n=10), OSE (n=7), and FTE (n=7) primary fresh-frozen tissues, and analyzed DNA methylome using Illumina 450K arrays (n=24) and Agilent Sure Select methyl-seq (n=7). We compared methylomes using statistical analyses of differentially methylated CpG sites (DMC) and differentially methylated regions (DMR), and methylation within a variety of different genomic contexts, including CpG island shores. We also analyzed methylation specifically at Homeobox (HOX) genes, due to their role in tissue specification. We used publically available HGSC methylome data (n=628) to provide additional comparison with FTE and OSE and potential validation. This analysis revealed that HGSC and FTE methylomes were significantly and consistently more highly conserved than were HGSC and OSE. Pearson correlations and hierarchal clustering of genes, promoters, CpG islands, CpG island shores, and HOX genes all revealed the increased relatedness of HGSC and FTE methylomes. In addition, two different large data sets of publically-available HGSC methylome data confirmed these relationships. In summary, our findings support the FTE origin model for HGSC, the most common and deadly EOC subtype. Due to its tissue-specificity and biochemical stability, interrogation of the DNA methylome appears to be a valuable approach to examine cell/tissue lineage in cancer.
2016-05-10 | GSE81227 | GEO
Project description:The cell and tissue of origin of high grade serous ovarian cancer (HGSC) is controversial. While the disease was traditionally assumed to arise from the ovarian surface epithelium (OSE), recent work supports an alternative model implicating the fallopian tube fimbriae epithelium (FTE). We used comparative DNA methylome analyses as a means to test these two competing models, hypothesizing that the HGSC methylome should more closely resemble its tissue of origin. Using two separate analysis methods, analysis within distinct genomic contexts, and validation studies using large-scale publically available HGSC methylome data, we consistently observed that the DNA methylome of HGSC more closely resembles FTE than OSE. These data support the FTE origin model, and suggest DNA methylome analysis as a useful approach to examine cell/tissue lineage origin in cancer. HGSC is the most common and lethal form of epithelial ovarian cancer (EOC). Two distinct tissues have been hypothesized as the tissue of origin of HGSC: OSE and FTE. We hypothesized that the DNA methylome of HGSC would more closely resemble the methylome of its tissue of origin. To test this, we profiled HGSC (n=10), OSE (n=7), and FTE (n=7) primary fresh-frozen tissues, and analyzed DNA methylome using Illumina 450K arrays (n=24) and Agilent Sure Select methyl-seq (n=7). We compared methylomes using statistical analyses of differentially methylated CpG sites (DMC) and differentially methylated regions (DMR), and methylation within a variety of different genomic contexts, including CpG island shores. We also analyzed methylation specifically at Homeobox (HOX) genes, due to their role in tissue specification. We used publically available HGSC methylome data (n=628) to provide additional comparison with FTE and OSE and potential validation. This analysis revealed that HGSC and FTE methylomes were significantly and consistently more highly conserved than were HGSC and OSE. Pearson correlations and hierarchal clustering of genes, promoters, CpG islands, CpG island shores, and HOX genes all revealed the increased relatedness of HGSC and FTE methylomes. In addition, two different large data sets of publically-available HGSC methylome data confirmed these relationships. In summary, our findings support the FTE origin model for HGSC, the most common and deadly EOC subtype. Due to its tissue-specificity and biochemical stability, interrogation of the DNA methylome appears to be a valuable approach to examine cell/tissue lineage in cancer.
2016-05-10 | GSE81224 | GEO
Project description:The transcriptomes of three immortalized ovarian surface epithelial cell lines (iOSE, PMID: 17266044) and primary OSE cells (Innoprot, Derio, Spain) and four immortalized fallopian tube secretory epithelial (iFTE) cell lines (PMID: 21502498, 22936217) were compared. RNA-sequencing was done from rRNA depleted total RNA (Ribo-Zero rRNA Removal Kit) to approx. 20 million 50 bp paired end reads per sample. A discriminative gene expression signature comprised of 211 genes was developed and used to classify isolated and EpCAM enriched primary ovarian cancer cells (PMID: 25991672). Impact of this signature on overall survival was assessed from several publicly available ovarian cancer gene expression data sets. Background: High grade serous ovarian cancer (HGSOC) is characterized by extensive local, i.e. peritoneal, tumor spread, manifested in two different clinical presentations, miliary (many millet sized peritoneal implants) and non-miliary (few large exophytically growing peritoneal nodes), and an overall unfavorable outcome. HGSOC is thought to arise from fallopian tube secretory epithelial cells, via so called serous tubal intraepithelial carcinomas (STICs) but an ovarian origin was never ruled out for at least some cases. Comparative transcriptome analyses of isolated tumor cells from fresh HGSOC tissues and (immortalized) ovarian surface epithelial and fallopian tube secretory epithelial cell lines revealed a close relation between putative origin and tumor spread characteristic, i.e. miliary from tubes and non-miliary from ovaries.
2016-12-15 | E-MTAB-5240 | biostudies-arrayexpress
Project description:Altered phosphatidylcholine (PC) metabolism in epithelial ovarian cancer (EOC) can provide choline-based imaging approaches as powerful tools to improve diagnosis and identify new therapeutic targets. Biochemical, protein and mRNA expression analyses demonstrated that the increase in the major choline-containing metabolite phosphocholine (PCho) in EOC compared with normal and non-tumoral immortalized counterparts (EONT) mainly rely upon: 1) ChoK activation, consistent with higher protein content and increased ChoK? mRNA expression levels; 2) PC-plc activation, consistent with higher, previously reported, protein expression. More limited and variable sources of PCho could derive, in some EOC cells, from activation of Phospholipase D or GPC-pd. Phospholipase A2 activity and isoforms’ expression levels were lower or unchanged in EOC compared with EONT cells. Increased ChoK? mRNA, as well as ChoK and PC-plc protein expression, were also detected in surgical specimens isolated from EOC patients. Overall, we demonstrated that the elevated PCho pool detected in EOC cells primarily resulted from the upregulation/activation of ChoK and PC-plc involved in the biosynthetic and in a degradative pathway of the PC-cycle, respectively. 20 EOC frozen surgical specimens, 8 EOC cell lines and Ovarian Surface Epithelial (OSE) cells (4 different preparations, 3 of them pooled in one sample).
2009-12-07 | E-GEOD-19352 | biostudies-arrayexpress
Project description:The purpose of this study is to evaluate the safety and one year disease-free survival of total or subtotal colectomy and proctocolectomy in stage IIIc and stage IV epithelial ovarian, fallopian tube, and primary peritoneal cancer (EOC, FTC, PPC).
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Project description:We profile expression in serous epithelial ovarian carcinomas to assess the possibility of an miRNA signature associated with chemoresistance. Resistance to the available therapies is one of the main causes of low survival of patients with advanced epithelial ovarian cancer, thus representing an emergency in oncology. Here, we profiled miRNA expression in 86 naïve serous epithelial ovarian carcinomas (EOCs) to assess the possibility of miRNAs associated with chemoresistance. We identified 23 miRNAs associated with chemoresistance, of which three (miR-484, miR-642 and miR-217) were confirmed in the validation set (112 independent patients). The study of miR-484 role demonstrated that it regulated the chemoresistance of EOC cells acting not on cancer cells but on tumor vasculature. In particular, miR-484 is produced and secreted by chemosensitive EOC, therefore regulating the production of VEGFB by cancer cells and the expression of VEGFR2 in endothelial cells. Overall, we demonstrated that a three-miR signature can classify the response to chemotherapy and that chemoresistance in EOC relays, at least in part, on the control of tumor angiogenesis, indicating new options in the treatment of these patients. We analyzed tumor samples (<5% of normal tissue) from FFPE blocks of 86 patients with serous ovarian carcinomas.
2013-05-17 | E-GEOD-43867 | biostudies-arrayexpress
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2010-01-20 | GSE19947 | GEO
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2018-05-25 | GSE108084 | GEO