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GSE31448
Homo sapiens
339 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
ECRG4 is a promising tumor suppressor gene (TSG) recently identified in esophageal carcinoma. Its expression and prognostic value have never been explored in breast cancer. Using DNA microarray, we examined ECRG4 mRNA expression in 353 invasive breast cancer samples. A meta-analysis was performed on a large public retrospective gene expression dataset (n=1,387) to analyze correlation between ECRG4 expression and histo-clinical features including survival.
Publication Title
Down-regulation of ECRG4, a candidate tumor suppressor gene, in human breast cancer.
Sample Metadata Fields
Age, Specimen part
View Samples- Bos taurus
- 3 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Ovarian follicular granulosa cells surround and nurture oocytes, and produce sex steroid hormones. It is believed that during development the ovarian surface epithelial cells invaginate into the ovary and develop into granulosa cells when associating with oogonia to form follicles. Using bovine fetal ovaries (n = 53) we identified a novel cell type, termed GREL for Gonadal Ridge Epithelial-Like. Using 25 markers for GREL and other cells we conducted immunohistochemistry and electron microscopy and chronologically tracked all somatic cell types during development. Before 70 days of gestation the gonadal ridge/ovarian primordium is formed by proliferation of GREL cells at the surface epithelium of the mesonephros. Primordial germ cells (PGCs) migrate into the ovarian primordium. After 70 days, stroma from the underlying mesonephros begins to penetrate the primordium, partitioning the developing ovary into irregularly-shaped ovigerous cords composed of GREL cells and PGCs/oogonia. Importantly we identified that the cords are separated from the stroma by a basal lamina. Around 130 days of gestation as the stroma expands laterally below the GREL cells on the surface thus establishing a sub-epithelial basal lamina and an epithelial-stromal interface, and it is at this stage that a mature surface epithelium develops from the GREL cells. The stroma continues to partition the ovigerous cords into smaller groups of cells eventually forming follicles containing an oogonium/oocyte surrounded by GREL cells, which become granulosa cells. Thus in contrast to the prevailing theory, the ovarian surface epithelial cells do not invaginate into the ovary to form the granulosa cells of follicles.
Publication Title
A new model of development of the mammalian ovary and follicles.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 19 Downloadable Samples
Illumina HiSeq 2000
Description
Background & Aims Hepatocytes differentiated from human embryonic stem cells (hESCs) have the potential to overcome the shortage of primary hepatocytes for clinical use and drug development. Many strategies for this process have been reported, but the functionality of the resulting cells is incomplete. We hypothesize that the functionality of hPSC-derived hepatocytes might be improved by making the differentiation method more similar to normal in vivo hepatic development. Methods We tested combinations of growth factors and small molecules targeting candidate signaling pathways culled from the literature to identify optimal conditions for differentiation of hESCs to hepatocytes, using qRT-PCR for stage-specific markers to identify the best conditions. Immunocytochemistry was then used to validate the selected conditions. Finally, induction of expression of metabolic enzymes in terminally differentiated cells was used to assess the functionality of the hESC-derived hepatocytes. Results Optimal differentiation of hESCs was attained using a 5-stage protocol. After initial induction of definitive endoderm (stage 1), we showed that inhibition of the WNT/ß-catenin pathway during the 2nd and 3rd stages of differentiation was required to specify first posterior foregut, and then hepatic gut cells. In contrast, during the 4th stage of differentiation, we found that activation of the WNT/ß-catenin pathway allowed generation of proliferative bipotent hepatoblasts, which then were efficiently differentiated into hepatocytes in the 5th stage by dual inhibition of TGF-ß and NOTCH signaling. Conclusion Here, we show that stage-specific regulation of the WNT/ß-catenin pathway results in improved differentiation of hESCs to functional hepatocytes. Overall design: mRNA profiles of undifferentiated, definitive endoderm, stage 2-5 cell ines were generated by deep sequencing, in duplicate, as well as five liver samples.
Publication Title
Stage-specific regulation of the WNT/β-catenin pathway enhances differentiation of hESCs into hepatocytes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina Genome Analyzer II
Description
Ribsome profiling analysis of mRNA translation in mouse cells under conditions of mTOR activiation or inhibition. Overall design: embryonic fibroblasts from 4EBP1/2 p53 mutants treated with Torin1
Publication Title
A unifying model for mTORC1-mediated regulation of mRNA translation.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
An understanding of the mechanisms regulating white adipose tissue (WAT) formation is key for developing of new tools to treat obesity and its related diseases. Here, we identify DEPTOR as a positive regulator of adipogenesis whose expression is associated with obesity. In a polygenic mouse model of obesity/leanness, Deptor is part of the Fob3a QTL linked to obesity and we fine that Deptor is the highest priority candidate gene regulating WAT accumulation in this model. Using a doxycycline-inducible mouse model for Deptor overexpression, we confirmed that Deptor promotes WAT expansion in vivo. DEPTOR expression is elevated in WAT of obese humans and strongly correlates with the degree of obesity. We show that DEPTOR is induced during adipogenesis and that its overexpression cell-autonomously promotes, while its suppression blocks, adipogenesis. DEPTOR positively regulates adipogenesis by promoting the activity of the pro-adipogenic factors Akt/PKB and PPAR-gamma. These results establish DEPTOR as a physiological regulator of adipogenesis and provide new insights into the molecular mechanisms controlling WAT formation.
Publication Title
DEPTOR cell-autonomously promotes adipogenesis, and its expression is associated with obesity.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2500
Description
The potential safety issues related to the acquisition of common genomic aberrations in hPSC cultures are well-recognized, but these risks have not been evaluated for sporadic mutations. Here, we explore whether a sporadic mutation that spontaneously arose in a hESC culture consisting of a single-copy deletion of chr17p13.1 would confer a survival advantage to the mutant cells. Compared to wild-type cells with two normal copies of the chr17p13.1 region, the mutant cells displayed a selective advantage when exposed to stressful conditions, and retained a higher percentage of pluripotent cells after two weeks of in vitro differentiation. Knockdown of TP53, which is a gene encompassed by the deleted region, in wild-type cells mimicked the chr17p13.1 deletion phenotype. RNA sequencing analysis showed differential expression of genes in pathways related to proliferation and differentiation. Thus, phenotypic implications of sporadic mutations must be taken into consideration before using the hPSC for clinical applications. Overall design: Triplicate cDNA libraries of two mutant WA09 lines with a single-copy deletion of chr17p13.1, and two wild-type WA09 lines, for a total of 12 libraries were sequenced using Illumina HiSeq 2500. The sequence reads were mapped to hg19 reference genome and hits that passed quality filters were analyzed for differential expression.
Publication Title
Spontaneous Single-Copy Loss of TP53 in Human Embryonic Stem Cells Markedly Increases Cell Proliferation and Survival.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 3 Downloadable Samples
- NextSeq 500
Description
We report single-cell transcriptional assessment and functional circuit characterization of neuron types within the mouse entopeduncular nucleus (EP) Overall design: Transcriptional profilingof EP neurons from P60-70 C57BL/6 male mice; three types were identified, characterized, and incorporated into a synaptic-circuit model of basal ganglia please note that Replicate 2 was lost experimentally and not included, so n=3 replicates total
Publication Title
Genetically Distinct Parallel Pathways in the Entopeduncular Nucleus for Limbic and Sensorimotor Output of the Basal Ganglia.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 265 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Medullary breast cancers (MBC) display a basal profile, but a favorable prognosis. We hypothesized that a previously published 368-gene expression signature associated with MBC might serve to define a prognostic classifier in basal cancers. We collected public gene expression and histoclinical data of 2145 invasive early breast adenocarcinomas. We developed a Support Vector Machine (SVM) classifier based on this 368-gene list in a learning set, and tested its predictive performances in an independent validation set. Then, we assessed its prognostic value and that of six prognostic signatures for disease-free survival (DFS) in the remaining 2034 samples. The SVM model accurately classified all MBC samples in the learning and validation sets. A total of 466 cases were basal across other sets. The SVM classifier separated them into two subgroups, subgroup 1 (resembling MBC) and subgroup 2 (not resembling MBC). Subgroup 1 exhibited 71% 5-year DFS, whereas subgroup 2 exhibited 50% (p=9.93E-05). The classifier outperformed the classical prognostic variables in multivariate analysis, conferring lesser risk for relapse in subgroup 1 (HR=0.52, p=3.9E-04). This prognostic value was specific to the basal subtype, in which none of the other prognostic signatures was informative.
Publication Title
A gene expression signature identifies two prognostic subgroups of basal breast cancer.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Long-lived, self-renewing, multipotent T memory stem cells (TSCM) can trigger profound and sustained tumor regression but their rareness poses a major hurdle to their clinical application. Presently, clinically compliant procedures to generate relevant numbers of this T cell population are undefined. Here, we provide a strategy for deriving large numbers of clinical grade tumor-redirected TSCM cells starting from nave precursors. CD8+CD62L+CD45RA+ nave T cells enriched by streptamer-based serial positive selection were activated by CD3/CD28 engagement in the presence of IL-7, IL-21 and the glycogen synthase-3 inhibitor TWS119, and genetically engineered to express a CD19-specific chimeric antigen receptor (CD19-CAR). These conditions allowed for the generation of CD19-CAR modified TSCM cells that were phenotypically, functionally and transcriptomically equivalent to their naturally occurring counterpart. Compared with T cell products currently under clinical investigation, CD19-CAR modified TSCM cells exhibit enhanced metabolic fitness, persistence and anti-tumor activity against systemic acute lymphoblastic leukemia xenografts. Based on these findings, we have initiated a phase 1 clinical study to evaluate the activity of CD19-CAR modified TSCM in patients with B-cell malignancies refractory to prior allogeneic hematopoietic stem cell transplantation.
Publication Title
Generation of clinical-grade CD19-specific CAR-modified CD8+ memory stem cells for the treatment of human B-cell malignancies.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina HiSeq 2500
Description
We used RNA sequencing to characterize gene expression of Ly75+/+ B1-8hi and Ly75-/- B1-8hi B cells from the germinal center light zone (LZ) 12 h after forcing positive selection of the Ly75+/+ population with anti-DEC205-OVA. Overall design: We primed C57BL/6 hosts with OVA-alum i.p. and after 2 weeks we adoptively transferred a mixture of B1-8hi B cells in which 15% were Ly75+/+ CD45.1 (DECP) and 85% were Ly75-/- CD45.1/2 (DECN). We then immunized the animals with NP-OVA in the footpads and after 6 days we injected anti-DEC205-OVA. 12 h or 24 h after anti-DEC205-OVA injection we sorted B220+ CD38- CD95+ CD45.1+ CD45.2- CD83hi CXCR4lo (DECPLZ) and B220+ CD38- CD95+ CD45.1+ CD45.2+ CD83hi CXCR4lo (DECNLZ) cells for whole transcriptome analysis by mRNA sequencing.
Publication Title
Germinal Center Selection and Affinity Maturation Require Dynamic Regulation of mTORC1 Kinase.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples