Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Global transcriptomic analysis of human pancreatic islets reveals novel genes influencing glucose metabolism [expression array]

ABSTRACT: Here we harnessed the potential of expression arrays in 89 human pancreatic islet donors (different levels of blood glucose (HbA1c)) to identify genes regulated in this relevant tissue for type 2 diabetes (T2D). Islets from cadaver donors were provided by the Nordic Islet Transplantation Programme (www.nordicislets.org), Uppsala University. The microarrays were performed using GeneChipM-BM-. Human Gene 1.0 ST whole transcript according to Affymetrix standard protocol.

ORGANISM(S): Homo sapiens

SUBMITTER: Joao Fadista

PROVIDER: E-GEOD-50397 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

TCF7L2 is a master regulator of insulin production and processing.

Zhou Yuedan Y Park Soo-Young SY Su Jing J Bailey Kathleen K Ottosson-Laakso Emilia E Shcherbina Liliya L Oskolkov Nikolay N Zhang Enming E Thevenin Thomas T Fadista João J Fadista João J Bennet Hedvig H Vikman Petter P Wierup Nils N Fex Malin M Rung Johan J Wollheim Claes C Nobrega Marcelo M Renström Erik E Groop Leif L Hansson Ola O

Human molecular genetics 20140711 24

Genome-wide association studies have revealed >60 loci associated with type 2 diabetes (T2D), but the underlying causal variants and functional mechanisms remain largely elusive. Although variants in TCF7L2 confer the strongest risk of T2D among common variants by presumed effects on islet function, the molecular mechanisms are not yet well understood. Using RNA-sequencing, we have identified a TCF7L2-regulated transcriptional network responsible for its effect on insulin secretion in rodent and ...[more]

PMID: 25015099

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Project description:The supply of red blood cells (RBCs) is not sufficient in many developing countries or in developed countries for patients who need chronic transfusion from best-matched donors. Ex vivo expansion and maturation of human erythroid precursor cells (erythroblasts) could represent a potential solution. Proliferating erythroblasts can be expanded from human umbilical cord blood mononuclear cells (CB MNCs) ex vivo for 10^6-10^7 fold (in ~50 days) before undergoing senescence. Here, we report that ectopic expression of three to four genetic factors that have been used for iPS cell derivation enables CB-derived erythroblasts to undergo extended ex vivo expansion (M-bM-^IM-%10^51 fold in ~9 months) in a defined suspension culture condition without change of cell identity or function. These vastly expanding erythroblasts maintain homogeneously immature erythroblast phenotypes, a normal diploid karyotype and dependence on specific combination of cytokines and hormone for survival and proliferation throughout the continuous expansion period. When switched to a culture condition for terminal maturation, these immortalized erythroblasts gradually exit cell cycle, decrease cell size, accumulate hemoglobin, condense nuclei and eventually give rise to enucleated hemoglobin-containing erythrocytes. Our result may ultimately lead to the development of unlimited sources of cultured RBCs for optimally-matched or personalized transfusion medicine. We compared the global gene expression profiles of different human cell types: iE: immortalized erythroblasts generated by genetic reprogramming from pCBE; pCBE: primary cord blood-derived erythroblasts; CD34+: CD34+ purified hematopoietic stem/progenitor cells from adult blood or fetal liver; TF-1: a human erythroleukemia cell line; ESC: human embryonic stem cells; iPSCs: human induced pluripotent stem cells. We want to see the relationship among these cell types. We included multiple samples (biological replicates) for most cell types.

Project description:Purpose: Due to the rarity of Merkel Cell Carcinoma (MCC), prospective clinical trials have not been practical. This study seeks to identify biomarkers to differentiate between patients with a good and poor prognosis. Methods: Patients were stratified into good, moderate or poor prognosis. Merkel cell carcinoma (MCC) patients were stratified into one of three groups based upon status 24 months following treatment. Poor prognosis patients either presented with or progressed to distant metastasis. Patients with favorable prognosis had local disease presentation with no subsequent recurrence or nodal disease at presentation with no progression during follow-up of longer than 24 months. Moderate prognosis had recurrent local disease, development of nodal metastasis, or nodal disease at presentation with no progression during follow-up of fewer than 24 months. Using ArcturusXT Laser Capture Microdissection (Molecular Devices), tumor cells were isolated from the specific areas of interest. The captured tumor tissue was subjected to RNA extraction using the Invitrogen PureLinkM-bM-^DM-" FFPE RNA Isolation Kit. The extracted RNA was analyzed for integrity with the Agilent Bioanalyzer then amplified and hybridized to Affymetrix GeneChip Human Exon 1.0 ST arrays using the NuGEN WT- OvationM-bM-^DM-" FFPE System. Results: A total of 191 genes showed significant differential expression (pM-bM-^IM-$0.05 and 1.5-fold cutoff) between the different between the good and poor prognosis groups. Keratin 20 (KRT20) and Neurofilament protein (NEFM) have been identified in previous studies as proteins of interest in MCC. Our study showed these genes to be significantly upregulated in patients with a poor prognosis. Of interest, phospholipase A2, group X was upregulated in poor responders. Phospholipases liberate arachidonic acid from cellular membranes which can be metabolized to eicosanoids through three major pathways: the cyclooxygenase (COX), the lipoxygenase (LOX) and the cytochrome P450 monooxygenase pathways. This pathway has been implicated in several cancers. Conclusions: The study identified genes with a previous association with MCC as well as some novel genes. These genes provide the basis for further research into possible biomarkers that will enable the differentiation between patients with a good and poor prognosis. Using laser capture microdissection, tumor cells of patients with a good (n=5), moderate (n=3), and poor prognosis (n=7) were isolated from paraffin embedded archival tissue of 15 patients with Merkel cell carcinoma. Affymetrix Human Exon 1.0ST microarrays were utilized to compare gene expression signatures from good and poor prognosis patients.

Dataset Information

Global transcriptomic analysis of human pancreatic islets reveals novel genes influencing glucose metabolism [expression array]

Publications

TCF7L2 is a master regulator of insulin production and processing.

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