Pancreatic islet transplantation as a cure for type 1 diabetes (T1D) cannot be scaled up due to a scarcity of human pancreas donors. In vitro expansion of beta cells from mature human pancreatic islets provides an alternative source of insulin-producing cells. The exact nature of the expanded cells produced by diverse expansion protocols, and their potential for differentiation into functional beta cells, remain elusive. We performed a large-scale meta-analysis of gene expression in human pancreatic islet cells, which were processed using three different previously described protocols for expansion and attempted re-differentiation. All three expansion protocols induced dramatic changes in the expression profiles of pancreatic islets; many of these changes are shared among the three protocols. Attempts at re-differentiation of expanded cells induce a limited number of gene expression changes. Nevertheless, these fail to restore a pancreatic islet-like gene expression pattern. Comparison with a collection of public microarray datasets confirmed that expanded cells are highly comparable to mesenchymal stem cells. Genes induced in expanded cells are also enriched for targets of transcription factors important for pluripotency induction. The present data increases our understanding of the active pathways in expanded and re-differentiated islets. Knowledge of the mesenchymal stem cell potential may help development of drug therapeutics to restore beta cell mass in T1D patients.
Meta-analysis of gene expression in human pancreatic islets after in vitro expansion.
Specimen part
View SamplesWe examined gene expression of LAPC4 cells after knocking down -TrCP, androgen ablation, or the combined treatments compared to non treated cells.
beta-TrCP inhibition reduces prostate cancer cell growth via upregulation of the aryl hydrocarbon receptor.
Cell line
View SamplesGene expression analysis of two different mouse keratinocytes using RNA-Seq Overall design: RNA was collected and analyzed for two biological replicates each from two different mouse keratinocyte cell lines
Evolutionary re-wiring of p63 and the epigenomic regulatory landscape in keratinocytes and its potential implications on species-specific gene expression and phenotypes.
Specimen part, Cell line, Subject
View SamplesAnalysis of gene expression changes during mouse salivary gland development using RNA-Seq Overall design: RNA was collected and analyzed for at least two biological replicates each from six developmental timepoints (E14.5, E16.5, E18.5, P5, 4 weeks, 12 weeks)
RNA-seq based transcriptomic map reveals new insights into mouse salivary gland development and maturation.
Age, Specimen part, Cell line, Subject
View SamplesAnalysis of gene-probe expression data (FPKM) for HNSCC cell-lines using single-end RNA-Seq Overall design: RNA was collected and analyzed from 6 HNSCC cell-lines ( SCC15, SCC4, SCC71, UMSCC103, UMSCC29, SCC351)
A global analysis of the complex landscape of isoforms and regulatory networks of p63 in human cells and tissues.
No sample metadata fields
View SamplesNote: GSE4063 and GSE4065 are not directly comparable.
Opposite transcriptional regulation in skeletal muscle of AMP-activated protein kinase gamma3 R225Q transgenic versus knock-out mice.
Sex, Specimen part
View SamplesAnalysis of AMPK gamma3-dependent transcriptional responses by analyzing global gene expression in the white portion of the gastrocnemius muscle in AMPK gamma3 mutant (R225Q) transgenic mice and corresponding wild type littermates.
Opposite transcriptional regulation in skeletal muscle of AMP-activated protein kinase gamma3 R225Q transgenic versus knock-out mice.
Sex, Specimen part
View SamplesAnalysis of AMPK gamma3-dependent transcriptional responses by analyzing global gene expression in the white portion of the gastrocnemius muscle in AMPK gamma3 knock-out mice and corresponding wild type littermates.
Opposite transcriptional regulation in skeletal muscle of AMP-activated protein kinase gamma3 R225Q transgenic versus knock-out mice.
Sex, Specimen part
View SamplesSince its discovery as a tumour suppressor some fifteen years ago, the transcription factor p53 has attracted paramount attention for its role as the guardian of the genome. TP53 mutations occur so frequently in cancer, regardless of patient age or tumour type, that they appear to be part of the life history of at least 50% of human tumours. In most tumours that retain wild-type p53, its function is inactivated due to deregulated HDM2, a protein which binds to p53 and which can inhibit the transcriptional activity of p53 and induce its degradation.
Ablation of key oncogenic pathways by RITA-reactivated p53 is required for efficient apoptosis.
Specimen part, Disease
View SamplesTargeting oncogene addiction is a promising strategy for anti-cancer therapy. Here, we report a potent inhibition of crucial oncogenes by p53 upon reactivation with small molecule RITA in vitro and in vivo. RITA-activated p53 unleashes transcriptional repression of anti-apoptotic proteins Mcl-1, Bcl-2, MAP4, and survivin, blocks Akt pathway on several levels and downregulates c-Myc, cyclin E and B-catenin. p53 ablates c-Myc expression via several mechanisms at transcriptional and posttranscriptional level. We show that transrepression of oncogenes correlated with higher level of p53 bound to chromatin-bound p53 than transactivation of pro-apoptotic targets. Inhibition of oncogenes by p53 reduces the cells ability to buffer pro-apoptotic signals and elicits robust apoptosis. Our study highlights the role of transcriptional repression for p53-mediated tumor suppression.
Ablation of key oncogenic pathways by RITA-reactivated p53 is required for efficient apoptosis.
No sample metadata fields
View Samples