Transcriptome analysis of arabinose fermentation by engineered Saccharomyces cerevisiae
Ontology highlight
ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae
SUBMITTER: Jean-Marc Daran
PROVIDER: E-GEOD-27539 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Acute myeloid leukemia (AML) with CEBPA mutations is determined as provisional entity in the current WHO. A difference in clinical outcome between single- (sm) and double-mutated (dm) cases has been reported, whereupon dm cases were shown to be associated with longer overall survival (OS). The occurrence and prognostic impact of concomitant molecular mutations in addition to CEBPAdm has not been assessed until now. Here, we investigated a cohort of 95 AML CEBPAdm cases for concomitant mutations. TET2 was found to be the most frequent mutation (32/94, 34.0%), followed by GATA2 (20/95, 21.0%), WT1 (13/95, 13.7%), DNMT3A (9/94, 9.6%), ASXL1 (9/95, 9.5%), NRAS (8/95, 8.4%), KRAS (3/94, 3.2%), IDH1/2 (6/95, 6.3%), FLT3-ITD (6/95, 6.3%), FLT3-TKD (2/95, 2.1%), NPM1 (2/95, 2.1%), and RUNX1 (1/94). No mutation was detected in MLL-PTD and TP53. With respect to prognostic impact, we observed that those cases harboring additional mutations in TET2 showed significant worse survival than wild-type cases (P=0.035), whereas GATA2 mutated cases showed improved survival (P=0.032). Further, using gene expression microarray analysis we identified no clear different clustering within the CEBPAdm cases with the distinct concomitant mutated genes. In conclusion, we demonstrated that 76.8% of CEBPAdm cases harbored additional alterations in other molecular markers and that CEBPA is a suitable MRD marker to control therapy. Total cohort contains 95 cases, but expression data available for 38 cases which were analyzed on Affymetrix HG-U133 Plus 2.0 arrays: 8 CEBPAdm and GATA2 mutated cases, 12 CEBPAdm and TET2 mutated cases, 7 CEBPAdm and ASXL1 mutated cases (n=3 showed an additional TET2 mutation) and 11 CEBPAdm without mutations in GATA2, TET2, and ASXL1.
2013-04-20 | E-GEOD-42064 | biostudies-arrayexpress
Project description:Multilineage dysplasia (MLD) has no impact on biological, clinico-pathological and prognostic features of AML with mutated nucleophosmin (NPM1) NPM1-mutated AML is a provisional entity in the WHO-2008 classification of myeloid neoplasms. The significance of concomitant multilineage dysplasia (MLD) in NPM1-mutated AML is unclear. Thus, in the WHO-2008 classification, NPM1-mutated AML with MLD is classified as AML with myelodysplasia(MD)-related changes. We evaluated the MLD impact in 378 NPM1-mutated AML patients. MLD was found in about 25% cases. Except for a lower WBC and FLT3-ITD incidence in MLD+ group, no significant differences were observed in age, sex, cytogenetics and FLT3-TKD between NPM1-mutated AML with and without MLD. Notably, NPM1-mutated AML with/without MLD showed overlapping immunophenotype (CD34-negativity) and GEP (CD34 downregulation and HOX genes upregulation). Moreover, OS and EFS did not differ among NPM1-mutated AML patients, independently of whether they carried or not MLD, the NPM1-mutated/FLT3-ITD negative cases showing the better prognosis. Lack of MLD impact on survival was confirmed by multivariate analysis that highlighted FLT3-ITD as the most significant prognostic parameter in NPM1-mutated AML. Our findings indicate that NPM1 mutations rather than MLD dictate the distinctive features of NPM1-mutated AML. Thus, irrespective of MLD, NPM1-mutated AML should be considered as one disease entity clearly distinct from AML with MD-related changes. These findings have important diagnostic and prognostic implications in AML. All bone marrow samples were obtained from untreated patients at the time of diagnosis. Cells used for microarray analysis were collected from the purified fraction of mononuclear cells after Ficoll density centrifugation. 48 samples
2010-07-30 | E-GEOD-18018 | biostudies-arrayexpress
Project description:To understand the developing striatum, key genes during development were identified using microarray analsyis tha could be considered as marker of medium spiny neurons. The ages studied is at peak striatal neurogenesis. 3 different gestational ages of CD1 mice were used with triplicate repeats
2016-06-23 | E-GEOD-55497 | biostudies-arrayexpress
Project description:Indole-3-carbinol is used as a dietary supplement and has potential use as a therapeutic agent for the prevention of various types of cancer. While substantial evidence exists that indole-3-carbinol can reduce the risk of cancers induced by several known carcinogens when administered to animals, indole-3-carbinol can also function as an initiator and tumor promoter in certain models. The carcinogenic potential of indole-3-carbinol has not been studied in a 2-year bioassay. The objective of the microarray study was to evaluate the transcriptional changes in liver from rats exposed to 0 or 300 mg/kg indole-3-carbinol. At 3 months, livers were analyzed from female Harlan Sprague Dawley rats in the 2-year gavage study of indole-3-carbinol. Female rats were administered 300 mg indole-3-carbinol/kg body weight in corn oil by gavage, 5 days per week in a 2 year toxicology study of indole-3-carbinol. Gene expression studies were performed on rat liver with samples hybridized to whole rat genome RG230_2.0 rat GeneChip arrays (Affymetrix, CA).
2014-07-17 | E-GEOD-59287 | biostudies-arrayexpress
Project description:We did transcription profiling on the effect of glucosamine in Saccharomyces cerevisiae using Research Genetics strains BY4741 (wild type) and 5251 (fks1). Yeast cells exposed to glucosamine in YPD growth medium show a significant increase in chitin content in the lateral cell wall. Likewise, cell wall stress caused by a gene deletion e.g., fks1 also results in elevated chitin. By comparing our data for fks1 with those from the literature we confirmed a strong induction of genes responsive to cell wall integrity, environmental stress as well as genes involved in cell signaling. Wild type cells treated with 15 mM glucosamine for 2 hours did not show any significant change in their transcription profile although the chitin level doubled during this time. For cells continuously exposed to glucosamine (steady state) there was a moderate transcription response, 105 genes showed a two-fold or higher change. The largest groups of up-regulated genes were those involved in mating, sporulation and cell cycle arrest. The largest group of down-regulated genes pertained to mitochondrial respiration. There was little overlap between those genes that have altered transcription from glucosamine treatment and those responsive to the fks1 mutation.
2007-07-07 | E-GEOD-441 | biostudies-arrayexpress
Project description:The multi-component global regulator Velvet complex has been identified as a key regulator of secondary metabolite production in Aspergillus and Penicillium species. Previous work indicated a massive impact of PcvelA and PclaeA deletions, two key components of the Velvet complex, on penicillin production in prolonged batch cultures of P. chrysogenum, as well as substantial changes in transcriptome. The present study investigates the impact of these mutations on product formation and genome-wide transcript profiles under glucose-limited, aerobic conditions, relevant for industrial production of ?-lactams. The gene-deletion cassette for PcvelA or PclaeA was integrated in a hdfA mutant of the penicillin high-producing strain P. chrysogenum DS17690. Predicted amino acid sequences of PcVelA and PcLaeA in this strain were identical to those in its ancestor Wisconsin54-1255. Controls were performed to rule out transformation-associated loss of penicillin-biosynthesis clusters which, in preliminary studies, led to a massive reduction of penicillin production in a PcvelA deletion mutant. The correct PcvelA and PclaeA deletion strains revealed a significant (up to 30 %) reduction of penicillin-G productivity relative to the reference strain, which is a much smaller reduction than previously reported for prolonged batch cultures of P. chrysogenum strains. Chemostat-based transcriptome analysis yielded only 23 genes with a consistent response in the PcvelA? and PclaeA? mutants when grown in the absence of the penicillin-G side-chain precursor phenylacetic acid. 11 of these genes belonged to two small gene clusters (with 5 and 6 genes, respectively), one of which contains a gene with high homology to an aristolochene synthase. These results provide a clear caveat that the impact of the Velvet complex on secondary metabolism in filamentous fungi may be strongly context dependent Previous studies on the impact of the Velvet complex in P. chrysogenum were performed in prolonged batch cultures. Time course analysis revealed that the impact of PcvelA and PclaeA mutations was most pronounced after prolonged incubation {Hoff, 2010 6 /id}, but the physiological status of these cultures was not precisely defined. Industrial production of ?-lactam antibiotics is performed in sugar-limited, aerobic fed-batch cultures {Menezes, 1994 76 /id}. The aim of the present study is to investigate the impact of the Velvet complex on physiology, penicilllin production and transcriptional regulation under industrially relevant conditions. To this end, we studied the impact of PcvelA and PclaeA deletions in aerobic, glucose-limited chemostat cultures of the penicillin high-producing strain P. chrysogenum DS17690.
2011-12-06 | E-GEOD-31633 | biostudies-arrayexpress
Project description:BCOR is a component of a variant Polycomb group repressive complex 1 (PRC1) complex. Recently, we and others reported recurrent somatic BCOR loss-of-function mutations in myelodysplastic syndrome and acute myelogenous leukaemia (AML). However the role of BCOR in normal hematopoiesis is largely unknown. Here, we explored the function of BCOR in myeloid cells using myeloid murine cell models with Bcor conditional loss-of-function or overexpression alleles. Bcor mutant bone marrow cells showed significantly higher proliferation and differentiation rates with reduced protein levels of RING1B, a ubiquitin ligase subunit of PRC1 family complexes. Global RNA expression profiling in murine cells and AML patient samples with BCOR loss-of-function mutation suggested that loss of BCOR expression is associated with proliferation and myeloid differentiation and decreased stem cell quiescence. Further, we used a MLL-AF9 murine model of AML and found that loss of Bcor increased serial replating efficiency, enhanced MLL-AF9 in blocking cell differentiation, and increased expression of Evi1 which is associated with leukemic transformation. Our results strongly suggest that BCOR plays an indispensable role in maintaining hematopoietic stem cell (HSC) quiescence by inhibiting myeloid stem cell proliferation and differentiation and offer a mechanistic explanation for how BCOR regulates gene expression such as Hox genes. Normal karyotype AML primary cells with either wild type BCOR (6 cases) or destructive mutated BCOR (6 cases) were collected and subjected to RNA expression microarray study
2015-12-31 | E-GEOD-69565 | biostudies-arrayexpress
Project description:Leukemic stem cells (LSC) might be the source for leukemic disease self-renewal and account for disease relapse after treatment, which makes them a critical target for further therapeutic options. Leukemia associated antigens (LAA) might be suitable structures to be attacked by immunotherapeutic agents. We performed primary AML sample enrichment and microarray studies to define LAA expression levels in AML. We compared the LAA expression in the enriched CD34+CD38- AML fraction to that of enriched HSC of healthy donors and AML bulk cells (CD34+CD38+, CD34-CD38+ and CD34-CD38). Furthermore, we investigated the expression patterns of co-stimulatory molecules in LSC, bulk AML cells and enriched HSC, Conclusion: We demonstrated the differential expression of several LAA in LSC, and their suitability as target structures. We enriched primary AML samples using CD34 and CD38 as markers to compare LAA expression levels of LSC, HSC and AML bulk. LAA expression profiles comparing LSC, HSC and leukemic bulk AML citation: Leukemic progenitor cells are susceptible to targeting by stimulated cytotoxic T cells against immunogenic leukemia-associated antigens Vanessa Schneider, Lu Zhang, Markus Rojewski, Natalie Fekete, Hubert Schrezenmeier, Alexander Erle, Lars Bullinger, Susanne Hofmann, Marlies Götz, Konstanze Döhner, Susann Ihme, Hartmut Döhner, Christian Buske, Michaela Feuring-Buske, Jochen Greiner
2015-04-23 | E-GEOD-68172 | biostudies-arrayexpress
Project description:Sustained Akt activation induces cardiac hypertrophy (LVH), which may lead to heart failure. This study tested the hypothesis that Akt activation contributes to mitochondrial dysfunction in pathological LVH. Akt activation induced LVH and progressive repression of mitochondrial fatty acid oxidation (FAO) pathways. Preventing LVH by inhibiting mTOR failed to prevent the decline in mitochondrial function but glucose utilization was maintained. Akt activation represses expression of mitochondrial regulatory, FAO, and oxidative phosphorylation genes in vivo that correlate with the duration of Akt activation in part by reducing FOXO-mediated transcriptional activation of mitochondrial-targeted nuclear genes in concert with reduced signaling via PPARα/PGC-1α and other transcriptional regulators. In cultured myocytes Akt activation disrupted mitochondrial bioenergetics, which could be partially reversed by maintaining nuclear FOXO, but not by increasing PGC-1α. Thus, although short-term Akt activation may be cardioprotective during ischemia by reducing mitochondrial metabolism and increasing glycolysis, long-term Akt activation in the adult heart contributes to pathological LVH in part by reducing mitochondrial oxidative capacity. Three samples per group of 8-week-old wild-type or transgenic mice with cardiac-specific constitutive expression of an activated Akt (caAkt) in the heart at 8 weeks of age were used. Mice have been previously described in depth (Shioi T, McMullen JR, Kang PM, Douglas PS, Obata T, Franke TF, Cantley LC, Izumo S. 2002. Akt/protein kinase B promotes organ growth in transgenic mice. Mol. Cell. Biol. 22:2799-2809.). After hearts were removed total myocardial RNA was labeled and processed as described below for microarray analysis to detail the global changes in gene expression underlying development of heart failure in this mouse model.
2015-01-05 | E-GEOD-63848 | biostudies-arrayexpress
Project description:The medial and cardiac lobes of the right lung and whole right lung of (initially) 10-12 week old C57BL/6 mice were transcriptome profiled at days 0, 3, 7, 14, 28 and 56 post left pneumonectomy, with day 0 being pre-pneumonectomy, and an additional day 56 post sham surgery to control for 8 week aging post left pneumonectomy. pneumonectomy time course
2013-08-09 | E-GEOD-39817 | biostudies-arrayexpress