Comparative FAIRE-seq analysis reveals distinguishing features of the chromatin structure of ground state- and primed pluripotent cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Matthew Murtha
PROVIDER: E-GEOD-58520 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Tumor suppressor p53 promotes differentiation of human embryonic stem cells (hESCs), but an in-depth understanding of mechanism is lacking. Here, we define p53 functions in hESCs by genome wide profiling of p53 chromatin interactions and intersection with gene expression during early differentiation and in response to DNA damage. During differentiation, p53 targets and regulates a unique collection of genes, many of which encode transcription factors and developmental regulators with chromatin structure poised by OCT4 and NANOG and marked by repressive H3K27me3 in pluripotent hESCs. In contrast, genes associated with cell migration and motility are bound by p53 specifically after DNA damage. Surveillance functions of p53 in regulation of cell death and cell cycle genes are conserved during both DNA damage and differentiation. Our findings expand the registry of p53 -regulated genes in hESCs and define specific functions of p53 in opposing pluripotency, which are highly distinct from stress-induced p53 response in stem cells. Identification of p53 binding sites in hESC under three conditions: Pluripotent, DNA damaged, Differentiating
2013-10-18 | E-GEOD-39762 | biostudies-arrayexpress
Project description:Tumor suppressor p53 promotes differentiation of human embryonic stem cells (hESCs), but an in-depth understanding of mechanism is lacking. Here, we define p53 functions in hESCs by genome wide profiling of p53 chromatin interactions and intersection with gene expression during early differentiation and in response to DNA damage. During differentiation, p53 targets and regulates a unique collection of genes, many of which encode transcription factors and developmental regulators with chromatin structure poised by OCT4 and NANOG and marked by repressive H3K27me3 in pluripotent hESCs. In contrast, genes associated with cell migration and motility are bound by p53 specifically after DNA damage. Surveillance functions of p53 in regulation of cell death and cell cycle genes are conserved during both DNA damage and differentiation. Our findings expand the registry of p53 -regulated genes in hESCs and define specific functions of p53 in opposing pluripotency, which are highly distinct from stress-induced p53 response in stem cells. Identification of p53 binding sites in hESC under three conditions : Pluripotent, DNA damaged, Differentiating
2013-10-18 | E-GEOD-39912 | biostudies-arrayexpress
Project description:Down syndrome (DS) is the most frequent cause of human congenital mental retardation. Cognitive deficits in DS result from perturbations of normal cellular processes both during development and in adult tissues, but the mechanisms underlying DS etiology remain poorly understood. To assess the ability of iPSCs to model DS phenotypes, as a prototypical complex human disease, we generated bona-fide DS and wild-type (WT) non-viral iPSCs by episomal reprogramming. DS iPSCs selectively overexpressed chromosome 21 genes, consistent with gene dosage, which was associated with deregulation of thousands of genes throughout the genome. DS and WT iPSCs were neurally converted at >95% efficiency, and had remarkably similar lineage potency, differentiation kinetics, proliferation and axon extension at early time points. However, at later time points DS cultures showed a two-fold bias towards glial lineages. Moreover, DS neural cultures were up to two times more sensitive to oxidative stress induced apoptosis, and this could be prevented by the anti-oxidant N-acetylcysteine. Our results reveal a striking complexity in the genetic alterations caused by trisomy-21 that are likely to underlie DS developmental phenotypes, and indicate a central role for defective early glial development in establishing developmental defects in DS brains. Furthermore, oxidative stress sensitivity is likely to contribute to the accelerated neurodegeneration seen in DS, and we provide proof of concept for screening corrective therapeutics using DS iPSCs and their derivatives. Non-viral DS iPSCs can therefore recapitulate features of complex human disease in vitro, and provide a renewable and ethically unencumbered discovery platform. Control (WT) and Down Syndrome iPSC lines were generated via episomal reprogramming of human donor fibroblasts. Two iPSC clones conforming to iPS criteria (determined by immunocytochemistry detection of pluripotency markers) were developed from each fibroblast donor. Two control (WT) and DS lines each were further characterized and underwent neural differentiation. Multiple biological replicates of donor fibroblast and iPSC from both control (WT) and DS lines, including 3 euploid DS samples and 3 MEL1 hESC controls (total 54 samples) were hybridized to Illumina HT-12 v4 microarray for gene expression analysis.
2012-12-17 | E-GEOD-42956 | biostudies-arrayexpress
Project description:Genomic profiling by array to find chromosomic region with aneuploidy in NPC and ESC clones from hybride C57BL5 and CAST mouse
2014-02-25 | E-MTAB-1823 | biostudies-arrayexpress
Project description:The main objectives of the project are as follows: 1) Deciphering the TIC specific secretome signature. The secretome collected from four different TICs and their corresponding differentiated cell cultures will be subjected to label-free quantitative proteomic analysis to identify a TIC specific secretome signature. 2) Validation and functional characterization of selected molecules from TIC specific secretome signature. Selected molecules based on the level of regulation and literature information will be validated at the level of transcript and protein. The importance of a set of validated proteins will be studied both in vitro using neurosphere cultures and angiogenesis assays, and in vivo using an intracranial glioma model in nude mice 3) Characterizing of GBM specific serum proteome signature. Using label-free quantitative proteomics, we will compare the serum proteome of tumor bearing mice (xenotransplantated with TICs), early after tumor establisment and after the tumor has reached its maximum size.We will also explore by targeted quantitative proteomics whether the level of “specific” TIC-secreted proteins is increased in the serum of TIC initiated GBM bearing mice and verify, using the same strategy, proteins found to be differentially expressed in serum in both mice groups. These studies will reveal whether TIC-secreted proteins (and/or other GBM-derived proteins) can be retrieved in serum and thus be considered as candidate biomarkers of GBM.
2022-06-07 | PXD032958 | Pride
Project description:The goal of this experiment is to identify autosomal random monoallelic gene in ESC and NPC from a C57BL6J x CAST hybrid
2014-02-26 | E-MTAB-1822 | biostudies-arrayexpress
Project description:Cellular differentiation involves widespread epigenetic reprogramming, including modulation of DNA methylation patterns. Using Differential Methylation Hybridization (DMH) in combination with a custom DMH array containing more than 53,000 features covering more than 16,000 murine genes, we carried out a genome-wide screen for cell- and tissue-specific differentially methylated regions (tDMRs) in undifferentiated embryonic stem cells (ESCs), in in-vitro induced neural stem cells (NSCs) and 8 differentiated embryonic and adult tissues. Unsupervised clustering of the generated data showed distinct cell- and tissue-specific DNA methylation profiles, revealing 202 significant tDMRs (p<0.005) between ESCs and NSCs and a further 380 tDMRs (p<0.05) between NSCs/ESCs and embryonic brain tissue. We validated these tDMRs using direct bisulfite sequencing (DBS) and methylated DNA immunoprecipitation on chip (MeDIP-chip). Gene ontology (GO) analysis of the genes associated with these tDMRs showed significant (absolute Z score >1.96) enrichment for genes involved in neural differentiation, including e.g. Jag1 and Tcf4. Our results provide robust evidence for the relevance of DNA methylation in early neural development and identify novel marker candidates for neural cell differentiation.
2012-03-22 | E-MTAB-576 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE16678: MicroRNA expression data from differentiation of human Cyt49 ESCs into definitive endoderm in feeder-free conditions GSE16681: mRNA expression data from differentiation of human ESCs into definitive endoderm, Cyt49 on matrigel GSE16687: MicroRNA expression data from differentiation of human Cyt49 ESCs into definitive endoderm on MEF feeder layers GSE16689: MicroRNA expression data from differentiation of human H9 ESCs into definitive endoderm on MEF feeder layers Refer to individual Series
2010-07-30 | E-GEOD-16690 | biostudies-arrayexpress
Project description:Background: The hES-T3 cell line with normal female karyotype was used to differentiate into autogeneic fibroblast-like cells (T3HDF) as feeder to support the undifferentiated growth of hES-T3 cells (T3/HDF) for 14 passages. A feeder-free culture on Matrigel in hES medium conditioned by these autogeneic feeder cells (T3HDF) was established to maintain the undifferentiated growth of hES-T3 cells (T3/CMHDF) for 8 passages. Results: The gene expression profiles of mRNAs, microRNAs and proteins between the undifferentiated T3/HDF and T3/CMHDF cells were shown to be very similar, and their expression profiles were also found to be similar to those of T3/MEF and T3/CMMEF cells grown on MEF feeder and feeder-free Matrigel in MEF-conditioned medium, respectively. The abundantly expressed genes of T3/HDF, T3/CMHDF, T3/MEF and T3/CMMEF cells were found to play prominent roles in signaling pathways and GO process networks. The miR-302/367 cluster and miR-371/372/373 cluster were extremely abundantly expressed in undifferentiated T3/HDF and T3/CMHDF as well as T3/MEF andT3/CMMEF cells. The undifferentiated state of T3/HDF and T3/CMHDF cells was evidenced by the very high expression levels of ¡§stemness¡¨ genes and low expression levels of differentiation markers of ectoderm, mesoderm and endoderm in addition to the strong staining of OCT4 and NANOG. Conclusion: The T3HDF feeder and T3HDF-conditioned medium were able to support the undifferentiated growth of hES cells, and they would be useful for drug development and toxicity testing in addition to the reduced risks of xenogeneic pathogens when used for medical applications such as cell therapies. Keywords: genetic modification In this investigation, both miRNA and mRNA expression profiles from human embryonic stem cells (hES-T3) grown on MEF feeder (T3_MEF), feeder-free Matrigel in MEF-conditioned medium (T3_CMMEF), T3HDF (hES-T3 differentiated fibroblast-like cells) feeder and feeder-free Matrigel in T3HDF-conditioned medium were quantitatively determined. Several target genes of T3BA and T3CM cells-specific miRNAs were identified. ***This submission represents the mRNA expression component of the study only***
2011-01-12 | E-GEOD-19902 | biostudies-arrayexpress
Project description:During early development before gonadal differentiation, sex chromosomes are the main difference between males and females. We examined any genetically driven sex dimorphisms in human pluripotent stem cells focusing on Y chromosome contribution. In order to understand the consequence of these differences, human ES cells were differentiated into EBs under the influence of Estrone (E1) and the global expression diffrences between male and females were examined. Male and female ES cells were differentiated by EB formation under E1 for RNA extraction and hybridization on Affymetrix GENE ST 1.0 microarrays (GPL6244). RNA was extracted at 0d 3d and 11d
2014-06-18 | E-GEOD-58591 | biostudies-arrayexpress