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Platform
GSE61867
Mus musculus
8 Downloadable Samples
Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
anti-CD4, CD8 and CD40L treated versus control murine CD4+ T cells from micegrafted with hESC derived xenografts.
Publication Title
Tolerance induction to human stem cell transplants with extension to their differentiated progeny.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
The oviducts contain high grade serous cancer precursors, which are -H2AXp and p53 mutation positive. Secretory cell outgrowths (SCOUTs) are associated with older age and serous cancer. We evaluated PAX2 expression in proliferating oviductal cells, normal mucosa, SCOUTs, Walthard cell nests, STINs and HGSCs. Non-ciliated cells in normal mucosa were PAX2 positive but became PAX2 negative in multilayered epithelium. PAX2 negative SCOUTs fell into two groups; Type I were secretory or secretory/ciliated with a tubal phenotype and were ALDH1 negative. Type II displayed a columnar to pseudostratified phenotype, with an EZH2,ALDH1, -catenin, Stathmin, LEF1, RCN1 and RUNX2 expression signature . This study, for the first time, links PAX2 negative with proliferating fetal and adult oviductal cells undergoing basal and ciliated differentiation and shows that this expression state is maintained in SCOUTs, STINs and HGSCs. All three entities can demonstrate a consistent perturbation of genes involved in potential tumor suppressor gene silencing (EZH2), transcriptional regulation (LEF1), regulation of differentiation (RUNX2) calcium binding (RCN1) and oncogenesis (Stathmin). This shared expression signature between benign and neoplastic entities links normal progenitor cell expansion to abnormal and neoplastic outgrowth in the oviduct and exposes a common pathway that could be a target of early prevention.
Publication Title
The PAX2-null immunophenotype defines multiple lineages with common expression signatures in benign and neoplastic oviductal epithelium.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
High-grade serous ovarian cancer (HGSOC) progresses to advanced stages without symptoms and the 5-year survival rate is a dismal 30%. Recent studies of ovaries and oviducts in patients with BRCA mutations revealed that premalignant HGSC is found almost exclusively in the fallopian tube. To validate this notion, we cloned and transformed the fallopian tube stem cells (FTSC). We demonstrated that the tumors derived from the transformed fallopian tube stem cells (FTSCt) share the similar histological and molecular feature of high-grade serous cancer. In addition, a whole-genome transcriptome analysis comparing between FTSC, immortalized fallopian tube stem cells (FTSCi), and FTSCt showing a clear molecular progression, which is mimicked by the gene expression comparison between laser captured normal oviducts and HGSOC ( cancer and paired normal samples from 10 patients).
Publication Title
In vitro and in vivo correlates of physiological and neoplastic human Fallopian tube stem cells.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
High-grade serous cancer (HGSC) progresses to advanced stages without symptoms and the 5-year survival rate is a dismal 30%. Recent studies of ovaries and fallopian tubes in patients with BRCA mutations revealed that pre-metastatic HGSC is found almost exclusively in the fallopian tube in a lesion termed serous tubal intraepithelial carcinoma or STIC. We have performed laser captured microdissection (LCM) of normal oviduct, STIC and invasive serous cancer from each patient. A whole-genome transcriptome analysis comparing between normal oviduct, STIC and invasive serous cancer were performed. We demonstrated a clear molecular progression from normal to STIC, which shared the gene expression patterns with invasive serous cancer, suggesting a new set of genes as basis of novel detection and therapeutic approaches to HGSC at its earliest stage.
Publication Title
In vitro and in vivo correlates of physiological and neoplastic human Fallopian tube stem cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
If the fallopian tube is the origin of serous cancer, one possible mechanism for the evolution of cancer is a dysregulation of indigenous stem cells. We therefore set out to clone the stem cells of the human fallopian tube using methods to clone columnar epithelial stem cells such as human intestinal stem cells. Using this method, we were able to generate clones of fallopian tube stem cells that contain many small, undifferentiated cells. These stem cell clones show strong and consistent staining with markers of fallopian tube epithelial cells (PAX8). We also established an air-liquid interface culture system to differentiate fallopian tube stem cell to both ciliated cells and non-ciliated cells.
Publication Title
In vitro and in vivo correlates of physiological and neoplastic human Fallopian tube stem cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 66 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Barretts esophagus confers significant risk of esophageal adenocarcinoma. We have established the cloning of patient-matched stem cells of Barretts, gastric, and esophageal epithelium. Barrett's esophagus stem cells (BE), gastric cardia stem cells (GC) and normal esophagus stem cells (Eso) from 12 patients were cloned (For BE: 12 patients, GC: 12 patients and Eso: 2 patients). Keratin 5 positive and Keratin 7 positive cells were cloned from human fetal esophageal epithelium. Using air liquid interface culture system, stem cells were induced to differentiate into mature epithelial structures.
Publication Title
Mutational spectrum of Barrett's stem cells suggests paths to initiation of a precancerous lesion.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Barretts esophagus confers significant risk of esophageal adenocarcinoma. We have established the cloning of patient-matched stem cells of Barretts, gastric, and esophageal epithelium. Transplantation of transformed Barretts stem cells yielded tumors with hallmarks of esophageal adenocarcinoma, whereas transformed esophageal stem cells produced squamous cell carcinomas. These findings define a stem cell target in a precancerous lesion for preemptive therapies.
Publication Title
Mutational spectrum of Barrett's stem cells suggests paths to initiation of a precancerous lesion.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Barretts esophagus is a precancerous lesion that confers a significant risk of esophageal adenocarcinoma. Strategies for selective eradication of Barretts have been stymied by our inability to identify the Barretts stem cell. Here we employ novel technologies to clone patient-matched stem cells of Barretts, gastric, and esophageal epithelium. Genomic analyses of Barretts stem cells reveal a patient-specific mutational spectrum ranging from low somatic variation similar to patient-matched gastric epithelial stem cells to ones marked by extensive heterozygous alteration of genes implicated in tumor suppression, epithelial planarity, and epigenetic regulation. Transplantation of transformed Barretts stem cells yields tumors with hallmarks of esophageal adenocarcinoma, whereas transformed esophageal stem cells yield squamous cell carcinomas. Thus Barretts develops from cells distinct from local eponymous epithelia, emerges without obvious driver mutations, and likely progresses through and from the generation of dominant clones. These findings define a stem cell target for preemptive therapies of a precancerous lesion.
Publication Title
Mutational spectrum of Barrett's stem cells suggests paths to initiation of a precancerous lesion.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 46 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cloning and variation of ground state intestinal stem cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Despite major advances with embryonic and induced pluripotent stem cells or lineage-committed, p63-expressing stem cells of stratified epithelia, we know less about the indigenous stem cells of the gastrointestinal tract, pancreas, liver, and other columnar epithelia which collectively resist cloning in their elemental states. Here we demonstrate the cloning of highly immature epithelial stem cells from defined regions of the human intestine and colon. We show that single cell-derived pedigrees can be propagated indefinitely while often sustaining minimal copy number and sequence variation. Despite prolonged cultivation, these pedigrees from disparate regions of the intestinal tract respond to identical differentiation signals by formation of epithelia with eponymous structural and gene expression features. These data suggest developmental patterning of cell-autonomous commitment programs in stem cells that enforce specialization along the gastrointestinal tract and predict the utility of these cells in disease modeling and regenerative medicine.
Publication Title
Cloning and variation of ground state intestinal stem cells.
Sample Metadata Fields
Specimen part
View Samples