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GSE11990
Mus musculus
20 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The epidermal specific ablation of Trp53 gene leads to the spontaneous development of aggressive tumors in mice through a process that is accelerated by the simultaneous ablation of Rb gene. Since alterations of p53-dependent pathway are common hallmarks of aggressive, poor prognostic human cancers, these mouse models can recapitulate the molecular features of some of these human malignancies. To evaluate this possibility, gene expression microarray analysis was performed in mouse samples. The mouse tumors display increased expression of cell cycle and chromosomal instability associated genes. Remarkably, they are also enriched in human embryonic stem cell gene signatures, a characteristic feature of human aggressive tumors. Using cross-species comparison and meta-analytical approaches, we also observed that spontaneous mouse tumors display robust similarities with gene expression profiles of human tumors bearing mutated TP53, or displaying poor prognostic outcome, from multiple body tissues. We have obtained a 20-gene signature whose genes are overexpressed in mouse tumors and can identify human tumors with poor outcome from breast cancer, astrocytoma and multiple myeloma. This signature was consistently overexpressed in additional mouse tumors using microarray analysis. Two of the genes of this signature, AURKA and UBE2C, were validated in human breast and cervical cancer as potential biomarkers of malignancy. Our analyses demonstrate that these mouse models are promising preclinical tools aimed to search for malignancy biomarkers and to test targeted therapies of prospective use in human aggressive tumors and/or with p53 mutation or inactivation.
Publication Title
Gene expression profiling of mouse p53-deficient epidermal carcinoma defines molecular determinants of human cancer malignancy.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus, Homo sapiens
- 51 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Bladder cancer (BC) is a highly prevalent human disease in which Rb pathway inactivation and epigenetic alterations are common events. However, the connection between these two processes is still poorly understood. Here we show that the in vivo inactivation of all Rb family genes in the mouse urothelium is sufficient to initiate BC development. The characterization of the mouse tumors revealed multiple molecular features of human BC, including the activation of E2F transcription factor and subsequent Ezh2 expression, and the activation of several signaling pathways previously identified as highly relevant in urothelial tumors. Whole transcriptional characterizations of the mouse bladder tumors revealed a significant overlap with human BC samples, and a predominant role for Ezh2 in the downregulation of gene expression programs. Importantly, we determined that in human superficial BC patients, the increased tumor recurrence and progression in these recurrences is associated with increased E2F and Ezh2 expression and Ezh2-mediated gene expression repression. Collectively, our studies provide a genetically defined model for human high-grade superficial BC and demonstrate the existence of an Rb-E2F-Ezh2 axis in bladder whose disruption can promote tumor development.
Publication Title
In vivo disruption of an Rb-E2F-Ezh2 signaling loop causes bladder cancer.
Sample Metadata Fields
Specimen part, Disease, Treatment
View Samples- Mus musculus
- 747 Downloadable Samples
Illumina HiSeq 2000
Description
Heterogeneous pools of adult neural stem cells (NSCs) contribute to brain maintenance and regeneration after injury. The balance of NSC activation and quiescence, as well as the induction of lineage-specific transcription factors, may contribute to diversity of neuronal and glial fates. To identify molecular hallmarks governing these characteristics, we performed single-cell sequencing of an unbiased pool of adult subventricular zone NSCs. This analysis identified a discrete, dormant NSC subpopulation that already expresses distinct combinations of lineage-specific transcription factors during homeostasis. Dormant NSCs enter a primed-quiescent state before activation, which is accompanied by downregulation of glycolytic metabolism, Notch, and BMP signaling and a concomitant upregulation of lineage-specific transcription factors and protein synthesis. In response to brain ischemia, interferon gamma signaling induces dormant NSC subpopulations to enter the primed-quiescent state. This study unveils general principles underlying NSC activation and lineage priming and opens potential avenues for regenerative medicine in the brain. Overall design: Single cell RNAseq of cells isolated from their in vivo niche in the subventricular zone, Striatum and Cortex during homeostasis as well as following ischemic injury. In total 272 single cells. (<WT>: homeostasis samples; <Ischemic_injured> and <Ischemic_injured_and_Interferon_gamma_knockout>: samples following ischemic injuried).
Publication Title
Single-Cell Transcriptomics Reveals a Population of Dormant Neural Stem Cells that Become Activated upon Brain Injury.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Transcripts upregulated or downregulated by HOXB7-MEK signaling were identified for use on the microarray using the Affymetrix GeneChip WT PLUS Reagent Kit in comparison with HOXB7-knockdown S2-013 cells that were transfected with rescue-HOXB7 plasmid and treated with MEK inhibitor, and HOXB7-knockdown S2-013 cells that were transfected with rescue-HOXB7 plasmid but not treated with MEK inhibitor.
Publication Title
The transcription factor HOXB7 regulates ERK kinase activity and thereby stimulates the motility and invasiveness of pancreatic cancer cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 88 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The biology underlying nodal metastasis is poorly understood. Transcriptome profiling has helped to characterize both primary tumors seeding nodal metastasis and the metastasis themselves. The interpretation of these data, however, is not without ambiguities. Here we profiled the transcriptomes of 17 papillary thyroid cancer (PTC) nodal metastases, associated primary tumors and primary tumors from N0 patients. We also included patient-matched normal thyroid and lymph node samples as controls to address some limits of previous studies. We found that the transcriptomes of patient-matched primary tumors and metastases were more similar than of unrelated metastases/primary pairs, a result also reported in other organ systems, and that part of this similarity reflected patient background. We found that the comparison of patient-matched primary tumors and metastases was heavily confounded by the presence of lymphoid tissues in the metastasis samples. An original data adjustment procedure was developed to circumvent this problem. It revealed a differential expression of stroma-related gene expression signatures also regulated in other organ systems. The comparison of N0 vs. N+ primary tumors uncovered a signal irreproducible across independent PTC datasets. This signal was also detectable when comparing the normal thyroid tissues adjacent to N0 and N+ tumors, suggesting a cohort specific bias also likely to be present in previous studies with similar statistical power. Classification of N0 vs. N+ yielded an accuracy of 63%, but additional statistical controls not presented in previous studies, revealed that this is likely to occur by chance alone. To address this issue, we used large datasets from The Cancer Genome Atlas and showed that N0 vs. N+ classification rates could not be reached randomly for most cancers. Yet, it was significant, but of limited accuracy (<70%) for thyroid, breast and head and neck cancers.
Publication Title
Revisiting the transcriptional analysis of primary tumours and associated nodal metastases with enhanced biological and statistical controls: application to thyroid cancer.
Sample Metadata Fields
Sex
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Arabidopsis Gene 1.0 ST Array (aragene10st)
Description
We established a novel in vitro tissue culture system (named VISUAL), in which xylem and phloem differentiation can be induced with Arabidopsis thaliana cotyledons
Publication Title
Vascular Cell Induction Culture System Using Arabidopsis Leaves (VISUAL) Reveals the Sequential Differentiation of Sieve Element-Like Cells.
Sample Metadata Fields
Age, Specimen part, Time
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Arabidopsis Gene 1.0 ST Array (aragene10st)
Description
We established a novel in vitro tissue culture system (named VISUAL), in which xylem and phloem differentiation can be induced with Arabidopsis thaliana cotyledons
Publication Title
Vascular Cell Induction Culture System Using Arabidopsis Leaves (VISUAL) Reveals the Sequential Differentiation of Sieve Element-Like Cells.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
BBF2H7 (BBF2 human homolog on chromosome 7), an ER-resident basic leucine zipper transcription factor, is activated in response to ER stress and abundantly expresses in chondrocytes. While BBF2H7 is widely expressed in many tissues and organs, the most intense signals were detected in the proliferating zone of the cartilage. We compared gene expressions in primary cultured chondrocytes prepared from rib cartilage between WT and BBF2H7-/- mice at E18.5. Primary cultured chondrocytes were prepared from E18.5 rib cartilage of WT and BBF2H7-/- mice. Chondrocytes were isolated using 0.2% collagenase D (Roche) after adherent connective tissue was removed by 0.2% trypsin (Sigma) and collagenase pretreatment. Isolated chondrocytes were maintained in -MEM (Gibco) supplemented with 10% FCS and 50 g/mL ascorbic acid. Adenovirus vectors expressing the mouse p60 BBF2H7 (1-377 aa, BBF-N) were constructed with the AdenoX Expression system (Clontech), according to the manufacturers protocol. The cells were infected with adenoviruses 30 h before analysis.
Publication Title
Regulation of endoplasmic reticulum stress response by a BBF2H7-mediated Sec23a pathway is essential for chondrogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 4000
Description
To comprehensively delineate the ontogeny of an organ system, we generated 112,217 single- cell transcriptomes representing all endoderm populations within the mouse embryo until midgestation. We employed graph-based approaches to model differentiating cells for spatio- temporal characterization of developmental trajectories. Our analysis reveals the detailed architecture of the emergence of the first (primitive or extra-embryonic) endodermal population and pluripotent epiblast. We uncover an unappreciated relationship between descendants of these lineages, before the onset of gastrulation, suggesting that mixing of extra-embryonic and embryonic endoderm cells occurs more than once during mammalian development. We map the trajectories of endoderm cells as they acquire embryonic versus extra-embryonic fates, and their spatial convergence within the gut endoderm; revealing them to be globally similar but retaining aspects of their lineage history. We observe the regionalized localization of cells along the forming gut tube, reflecting their extra-embryonic or embryonic origin, and their coordinate patterning into organ-specific territories along the anterior-posterior axis. Overall design: Total RNA was extracted from bulk tissue and dissociated cells of 13ss (~E8.75) gut tubes, from bulk tissue from anterior, anterior-midgut, midgut-posterior and posterior sections of 13ss gut tubes, as well as from extra-embryonic visceral endoderm and embryonic visceral endoderm of E7.5 embryos (see also table in section: Bulk RNA processing). The Trizol method (Invitrogen) was used for RNA extraction.
Publication Title
The emergent landscape of the mouse gut endoderm at single-cell resolution.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Low levels of the cell cycle regulator p27Kip1 are associated with a worse outcome in many tumor types. We report here a new regulatory role of p27Kip1 as a transcriptional regulator. In association with transcriptional factors such as ETS and E2F4 and co-repressors like p130, HDACs and mSin3A, p27 binds to promoters of multiple genes leading to their repression. The p27-target genes participate in RNA processing, translation, respiration and cell cycle. Remarkably, p27-target genes are over-expressed in different human tumors in tight association with a poor clinical prognosis. We also observed a clear correlation between low levels of p27 and over-expression of p27-target genes in tumors. Overall, our findings indicate new tumor suppressor roles of p271 as a transcriptional regulator of genes relevant for oncogenesis.
Publication Title
p27Kip1 represses transcription by direct interaction with p130/E2F4 at the promoters of target genes.
Sample Metadata Fields
Specimen part
View Samples