Modeling Fanconi Anemia pathogenesis and therapeutics using integration-free patient iPSCs
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Nuria Montserrat
PROVIDER: E-GEOD-57828 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:We compared the epigenetic status of the mutant and disease-free iPSCs at the whole genome level. Whole epigenome profiling based on trimethylated H3K4 (H3K4me3) showed concordant epigenetic remodeling in the two corrected clones when compared with two mutant iPSC clones. Examination of genome-wide gene expression in Fanconi anemia patient iPSCs before and after gene correction
2014-05-21 | E-GEOD-57826 | biostudies-arrayexpress
Project description:We compared the epigenetic status of the mutant and disease-free iPSCs at the whole genome level. Whole epigenome profiling based on trimethylated H3K4 (H3K4me3) showed concordant epigenetic remodeling in the two corrected clones when compared with two mutant iPSC clones. Examination of the trimethylated H3K4 histone modification in Fanconi anemia patient iPSCs before and after gene correction
2014-05-21 | E-GEOD-57827 | biostudies-arrayexpress
Project description:The protein p27(Kip1), a member of the Cip-Kip family of cyclin-dependent kinase inhibitors, has been recently identified as a transcriptional regulator. However, the transcriptional programs regulated by this protein, still remain mostly unknown. The aim of this study has been to define the transcriptional programs regulated by p27 by first identifying the p27-binding sites on the whole chromatin of quiescent mouse embryonic fibroblasts by Chromatin Immunoprecipitation Sequencing (ChIP-seq). Results revealed that most of the p27 binding sites were in distal intergenic regions and introns whereas, in contrast, its association with promoter regions was very low. Gene ontology analysis of the protein coding genes revealed a number of relevant transcriptional programs regulated by p27 as cell adhesion, intracellular signalling and neuron differentiation among others. We validated the interaction of p27 with different chromatin regions by ChIP followed by qPCR and demonstrated that the expressions of several genes belonging to these programs are actually regulated by p27.
2017-02-21 | E-MTAB-5105 | biostudies-arrayexpress
Project description:DYRK1A is a dosage-sensitive protein kinase that fulfills key roles during development and in tissue homeostasis, and its dysregulation results in human pathologies. DYRK1A is present in both the nucleus and cytoplasm of mammalian cells, although its nuclear function remains unclear. Genome-wide analysis of DYRK1A-associated loci reveals that the kinase is recruited preferentially to promoters of genes actively transcribed by RNA polymerase II (RNAPII), which are functionally associated with translation, RNA processing and cell cycle. DYRK1A-bound promoter sequences are highly enriched in a conserved palindromic motif, which is necessary to drive DYRK1A-dependent transcriptional activation. DYRK1A phosphorylates the carboxy-terminal domain (CTD) of RNAPII at Ser2 and Ser5. Depletion of DYRK1A results in reduced association of RNAPII at the target promoters as well as hypophosphorylation of the CTD of RNAPII along the target gene bodies. Accordingly, we propose that DYRK1A acts as a transcriptional regulator by acting as a novel CTD kinase. Occupancy of the kinase DYRK1A in two different cell lines and in two different growing conditions.
2015-03-11 | E-GEOD-63712 | biostudies-arrayexpress
Project description:Hepatitis C virus (HCV) remains a significant public health threat as new 1.75 million HCV infections emerged worldwide. The majority of these infections become persistently infected, while around 30 % spontaneously eliminate the virus. Clinical factors for viral clarification are related to HCV interaction with host immune system, but little is known about the consequences after HCV spontaneous resolution. These individuals are difficult to recruit and study as acute infection is usually asymptomatic, and they will not be identified unless it progress to chronic infection. The study of peripheral blood mononuclear cells (PBMCs) of these patients is crucial, as PBMCs are one of the main HCV extrahepatic reservoirs, and its transcriptional profile provide us information of innate and adaptive immune response against HCV infection. Our research shows novel insight on molecular consequences of spontaneous resolution after an acute HCV infection. 96 Individuals with different HCV exposure status were recruited: spontaneous resolved, chronic infected and healthy controls; and the microRNA profile of their PBMCs were analyzed. Our results indicate similar disruption of miRNA expression on HCV chronic patients and those who spontaneously clarified the infection, compared to control patients. The disrupted miRNAs formed a signature of 21 miRNAs that mainly regulate lipid metabolism. This is the first report showing miRNA profile similarities between chronic HCV patients and spontaneous resolved individuals. Thus, our results suggest that HCV infection promotes molecular alterations in PBMCs that will last longer after HCV spontaneous eradication. This evidences open up new prospects in the management of individuals who spontaneously clarified infection, as they should be monitored and followed to dismiss future HCV-related complications, such us liver diseases complications. The identified miRNA signature could be used as biomarker to monitor HCV fingerprint on HCV-exposed patients.
2019-06-21 | E-MTAB-8023 | biostudies-arrayexpress
Project description:We have carried out a longitudinal study of PBMC's miRNA profile in HIV/HCV coinfected patients (n=28) after HCV eradication with DAA and SVR achivement. HIV monoinfected patients (n=16) were used as control. Briefly, peripheral venous blood samples were collected in EDTA tubes, and PBMCs were isolated within the first 4 hours after extraction.Total RNA including miRNAs were isolated from PBMCs with the miRNeasy Mini kit (Qiagen). Quality and integrity were evaluated by the Bioanalyzer 2100 with Agilent RNA 6000 Nano kit (Agilent). Only those samples with RIN > 7.5 were sequenced. Small RNA library synthesis and sequencing were performed at Centre for Genomic Regulation (CRG) at Barcelona (Spain). Small RNA libraries were constructed with Illumina’s TruSeq Small RNA kit v.4 (Illumina) and 50nts (1x50) were sequenced in an Illumina HiSeq2500, with a single read approach.
2021-11-23 | E-MTAB-10566 | biostudies-arrayexpress
Project description:A total of 117 HIV-1 infected patients were analyzed. These individuals were categorized in three different groups according to their infectious status for HCV: A) HIV+/HCV+ group, (n=45) patients with HIV infection and active HCV-chronic infection naïve to any HCV treatment (positive PCR and positive HCV antibodies); B) HIV+/HCV- group, (n=36) patients who had been exposed to HCV but experienced spontaneous viral clearance during the first 6 months after HCV infection (negative PCR and positive HCV antibodies); C) HIV+ group, (n=36) HIV+ mono-infected patients that had never been infected with HCV (negative PCR, negative HCV antibody and no previous HCV treatment). Briefely, peripheral venous blood samples were collected in EDTA tubes, and PBMCs were isolated within the first 4 hours after extraction.Total RNA including miRNAs were isolated from PBMCs with the miRNeasy Mini kit (Qiagen). Quality and integrity were evaluated by the Bioanalyzer 2100 with Agilent RNA 6000 Nano kit (Agilent). Only those samples with RIN > 7.5 were sequenced. Small RNA library synthesis and sequencing were performed at Centre for Genomic Regulation (CRG) at Barcelona (Spain). Small RNA libraries were constructed with Illumina’s TruSeq Small RNA kit v.4 (Illumina) and 50nts (1x50) were sequenced in an Illumina HiSeq2500, with a single read approach.
2021-11-23 | E-MTAB-8274 | biostudies-arrayexpress
Project description:Investigation of the effects of UNR (CSDE1) knock-down on transcript levels of Melanoma Cells.
2016-10-31 | E-MTAB-3805 | biostudies-arrayexpress
Project description:Maternal 5-HT1A-receptor (R) is required for the timely development of the hippocampus and the establishment of emotional behaviors in Swiss-Webster (SW) mice. A partial and/or complete loss of maternal 5-HT1AR results in delayed ventral dentate granule cell (v-DGC) development and subsequent anxiety-like phenotype in the wild-type offspring by a non-genetic, presumably epigenetic mechanism. Here we tested v-DGCs for genome-wide DNA methylation changes elicited by the receptor deficient maternal environment. We identified a set of hypomethylated regions in the offspring of receptor deficient mothers. A significant fraction of these maternal-differentially methylated regions (m-DMRs) mapped to strong CpG islands, sequences that are typically not methylated or if methylated, resistant to environmental-induced changes. Many m-DMRs mapped to exons and some were associated with expression changes. Their hypomethylation was due to an arrest in de novo methylation and, to a lesser extent, to demethylation during postnatal life indicating that the perturbation in methylation coincides with the developmental delay in DGC maturation in the offspring of receptor deficient mothers. Inhibiting methylation in differentiating neurons impaired their maturation further suggesting a link between de novo methylation and neuronal differentiation. These data suggest that methylation at specific exonic CpG-islands may contribute to the mechanism through which maternal 5-HT1AR modulates hippocampal development and consecutively the level of anxiety in the SW offspring. Reduced 5-HT1AR-binding has been reported in individuals, particularly in association with anxiety/depression, including peri/postpartum depression. Therefore, maternal receptor deficit may contribute, via a non-genetic mechanism, to the high prevalence and heritability of anxiety disorders in human. Examined 4 samples: 5HT1A wild type offspring with 5HT1A wild type/heterozygous mother or 5HT1A KO offspring with 5HT1A of heterozygous/knock out mother
2013-02-04 | E-GEOD-35854 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-02-01 | E-GEOD-39217 | biostudies-arrayexpress