Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

41 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genome-wide maps of DNA cytosine methylation state in during normal differentiation commitment in hematopoietic stem cells (HSC) and in Special AT-rich sequence-binding protein1 (Satb1) - deficient HSC

ABSTRACT: Our data show Satb1 deficiency leads to alterations in DNA cytosine methylation and a commitment-primed epigenetic state in HSCs. Examination of DNA cytosine methylation in wild type HSC and differentiation-committed progenitors as well as in wild type HSC and HSC lacking Satb1 (n=2 each).

ORGANISM(S): Mus musculus

SUBMITTER: Boris Bartholdy

PROVIDER: E-GEOD-44304 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Publications

Satb1 regulates the self-renewal of hematopoietic stem cells by promoting quiescence and repressing differentiation commitment.

Will Britta B Vogler Thomas O TO Bartholdy Boris B Garrett-Bakelman Francine F Mayer Jillian J Barreyro Laura L Pandolfi Ashley A Todorova Tihomira I TI Okoye-Okafor Ujunwa C UC Stanley Robert F RF Bhagat Tushar D TD Verma Amit A Figueroa Maria E ME Melnick Ari A Roth Michael M Steidl Ulrich U

Nature immunology 20130407 5

How hematopoietic stem cells (HSCs) coordinate the regulation of opposing cellular mechanisms such as self-renewal and differentiation commitment remains unclear. Here we identified the transcription factor and chromatin remodeler Satb1 as a critical regulator of HSC fate. HSCs lacking Satb1 had defective self-renewal, were less quiescent and showed accelerated lineage commitment, which resulted in progressive depletion of functional HSCs. The enhanced commitment was caused by less symmetric sel ...[more]

PMID: 23563689

Similar Datasets

Novel IDH1 Mutant Inhibitors for Treatment of Acute Myeloid Leukemia (ERRBS)

Project description:Neomorphic mutations in isocitrate dehydrogenase 1 (IDH1) are driver mutations in acute myeloid leukemia (AML) and other cancers. We report the development of new allosteric inhibitors of mutant IDH1. Crystallographic and biochemical results demonstrated that compounds of this chemical series bind to an allosteric site and lock the enzyme in a catalytically inactive conformation, thereby enabling inhibition of different clinically relevant IDH1 mutants. Treatment of IDH1 mutant primary AML cells uniformly led to a decrease in intracellular 2-HG, abrogation of the myeloid differentiation block and induction of granulocytic differentiation at the level of leukemic blasts and more immature stem-like cells, in vitro and in vivo. Molecularly, treatment with the inhibitors led to a reversal of the DNA cytosine hypermethylation patterns caused by mutant IDH1 in AML patients’ cells. Our study provides proof-of-concept for the molecular and biological activity of novel allosteric inhibitors for targeting different mutant forms of IDH1 in leukemia. To obtain insight into the molecular mechanism of the novel IDH1 mutant allosteric inhibitor, primary AML cells were treated with either GSK321 IDH1 active inhibitor or Controls (DMSO or GSK990 inactive inhibitor) followed by DNA extraction for ERRBS analysis. Primary IDH1 mutant acute myeloid leukemia (AML) mononuclear (MNC) cells were treated in suspension cultures in differentiating media for 6 days with 3 microM GSK990 or GSK321 and an equal volume of DMSO, Followed ERRBS analysis after DNA extraction.

2015-09-21 | E-GEOD-72247 | biostudies-arrayexpress

Cell of origin determines clinically relevant subtypes of MLL-rearranged AML

Project description:MLL-fusion proteins can induce acute myeloid leukemias (AML) from either hematopoietic stem cells (HSC) or granulocyte macrophage progenitors (GMP), but it remains unclear if the cell of origin influences the biology of the resultant leukemia. MLL-AF9 transduced single HSC or GMP could be continuously replated, but HSC-derived clones were more likely than GMP-derived clones to initiate AML in mice. Leukemia stem cells derived from either HSC or GMP had a similar immunophenotype consistent with a maturing myeloid cell (LGMP). Gene expression analyses demonstrated that LGMP inherited gene expression programs from the cell of origin including high-level Evi-1 expression in HSC derived LGMP. The gene expression signature of LGMP derived from HSC was enriched in poor prognosis human MLL-rearranged AML in three independent data sets. Moreover, global 5’-mC levels were elevated in HSC-derived leukemias as compared to GMP-derived leukemias. This mirrored a difference seen in 5-mC between MLL-rearranged human leukemias that are either EVI1-positive or EVI1-negative. Finally, HSC derived leukemias were more resistant to chemotherapy than GMP-derived leukemias. These data demonstrate that the cell of origin influences the gene expression profile, the epigenetic state, and the drug response in AML, and that these differences can account for clinical heterogeneity within a molecularly defined group of leukemias. Differential DNA methylation between of LSC isolated from murine HSC and GMP derived AMLs

2013-01-09 | E-GEOD-43333 | biostudies-arrayexpress

Specific molecular signatures underlie response to decitabine in CMML [ERRBS]

Project description:Myelodysplastic syndromes and chronic myelomonocytic leukemia (CMML) are characterized by mutations in epigenetic modifiers and aberrant DNA methylation. DNA methyltransferase inhibitors (DMTis) are used to treat these disorders, but response is highly variable with few means to predict which patients will benefit. To develop a molecular means of predicting response at diagnosis, we examined baseline differences in mutations, DNA methylation, and gene expression in 40 CMML patients responsive and resistant to decitabine (DAC). While somatic mutations did not differentiate responders and non-responders, we were able to identify for the first time 158 differentially methylated regions (DMRs) at baseline between responders and non-responders using next-generation sequencing. These DMRs were primarily localized to non-promoter regions and overlapped with distal regulatory enhancers. Using the methylation profiles, we developed an epigenetic classifier that accurately predicted DAC response at the time of diagnosis. We also found 53 differentially expressed genes between responders and non-responders. Genes up-regulated in responders were enriched in the cell cycle, potentially contributing to effective DAC incorporation. Two chemokines overexpressed in non-responders -- CXCL4 and CXCL7 -- were able to block the effect of DAC on normal CD34+ and primary CMML cells in vitro, suggesting their up-regulation contributes to primary DAC resistance. DNA methylation profiling in bone marrow mononuclear cells (BM MNC) from 39 CMML patients (19 decitabine responders vs. 20 non-responders).

2015-03-31 | E-GEOD-61161 | biostudies-arrayexpress

Epigenomic alterations in localized and advanced prostate cancer

Project description:Here we used Illumina NGS for high-throughput profiling of the DNA methylome in seven human benign prostate tissues, seven human primary prostate cancer and six human castration resistant prostate cancer patient samples. These data were used to profile the CpG cytosine methylation pattern at single base resolution in each sample and to determine differentially methylated cytosines and regions among samples. Enhanced Reduced Representation Bisulfite Sequencing (ERRBS, MspI,150M-bM-^@M-^S400 bp size fractions) of 20 human prostate tissues (benign prostate tissues, localized and metastatic prostate cancer)

2013-07-03 | E-GEOD-41701 | biostudies-arrayexpress

Idh1-R132H mutation increases murine hematopoietic progenitors and alters epigenetics.

Project description:Mutations in the IDH1 and IDH2 genes encoding isocitrate dehydrogenases are frequent in human glioblastomas1 and cytogenetically normal acute myeloid leukemias (AML)2. These alterations are gain-of-function mutations in that they drive the synthesis of the M-bM-^@M-^\oncometaboliteM-bM-^@M-^] R-2-hydroxyglutarate (2HG)3. It remains unclear how IDH1 and IDH2 mutations modify myeloid cell development and promote leukemogenesis. Here we report the characterization of conditional knock-in mice in which the most common IDH1 mutation, Idh1-R132H, is inserted into the endogenous murine Idh1 locus and is expressed in cells of the hematopoietic (Vav-KI) or more specifically in cells of the myeloid (LysM-KI) lineage. These mutants show increased numbers of early hematopoietic progenitors and develop splenomegaly and anemia with extramedullary hematopoiesis, suggesting a dysfunctional bone marrow niche. Furthermore, LysM-KI cells exhibit both hypermethylated histones and changes to DNA methylation similar to those observed in human IDH1/2-mutant AML. Thus, our study is the first to describe the generation of conditional Idh1-R132H-KI mice. Furthermore, our study is also the first report showing the induction of a leukemic DNA methylation signature in a modeled system and sheds light on the mechanistic links between IDH1 mutation and human AML. DNA methylation profiling in LSK cells from IDH1-R132H knock-in mice vs. control mice

2012-07-22 | E-GEOD-38687 | biostudies-arrayexpress

methylSig: a whole genome DNA methylation analysis pipeline

Project description:DNA methylation plays critical roles in gene regulation and cellular specification without altering DNA sequences. The wide application of reduced representation bisulfite sequencing (RRBS) and whole genome bisulfite sequencing (bis-seq) opens the door to study DNA methylation at single CpG site resolution. One challenging question is how best to test for significant methylation differences between groups of biological samples in order to minimize false positive findings. Current methods to analyze genome-wide bisulfite sequencing data use a smoothing approach or a simple statistical test based on the binomial distribution. Comparative DNA methylation profiling in AML blasts and normal CD34(+) control cells

2014-08-22 | E-GEOD-55569 | biostudies-arrayexpress

Base-pair resolution DNA methylation sequencing reveals profoundly divergent epigenetic landscapes in Acute Myeloid Leukemia

Project description:Here we used Illumina NGS for high-throughput profiling of the DNA methylome in two human colon cancer derived cell lines, two human normal bone marrow CD34+ controls and in five human Acutre Myeloid Leukeima patient samples. These data can be used to determine the CpG cytosine methylation pattern at base pair resolution in each sample and to determine differentially methylated cytosines and regions between samples Reduced Representation Bisulfite Sequencing (RRBS) and Extended Reduced Representation Bisulfite Sequencing (ERRBS) on genomic DNA. We used colon cancer cell lines (two) to establish reproducbility and range of assay sensitivity. We used Acute Myeloid Leukemia patient samples and CD34+ bone marrow cells as controls to determine the methylome pattern in the patient samples

2012-06-01 | E-GEOD-37454 | biostudies-arrayexpress

Tet proteins in DNA demethylation and cell fate restriction

Project description:DNA methylation at 5-position of cytosine (5mC) is one of the best studied epigenetic modifications that plays important roles in diverse biological processes. Iterative oxidation of 5mC by the Ten-eleven translocation (Tet) family of proteins generates 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC), which can be further processed by DNA repair proteins leading to DNA demethylation. Functional characterization of the Tet proteins has been complicated by the redundancy between the three Tet proteins. Using the CRISPR/Cas9 technology, we have generated mouse embryonic stem cells (ESCs) deficient for all three Tet proteins (TKO). Whole genome bisulphite sequencing (WGBS) analysis revealed that Tet-mediated DNA demethylation mainly occurs distal enhancers as well as promoters that significantly overlap with 5hmC, 5fC and 5caC. Characterization of the Tet TKO ESCs revealed a function for Tet proteins in cell fate restriction as Tet TKO ESCs tend to adopt both primed pluripotent stem cell-like state and 2-cell embryo-like state. In addition, Tet TKO ESCs exhibit elongated telomeres. Thus, our study reveals a role of Tet proteins not only in DNA demethylation, but also in cell fate restriction and telomere maintenance. 2 samples for WGBS and 2 samples for RNA-seq

2014-09-22 | E-GEOD-56986 | biostudies-arrayexpress

Promoter methylome and integrative transcriptome profiling identify key epigenetics-regulated genes in human HCCs [methylation]

Project description:Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers worldwide and has a poor prognosis. Promoters represent an essential regulatory element of gene transcription in the human genome. In order to understand the promoter methylation in relation with gene transcription in HCCs, we applied a liquid hybridization capture-based bisulfite sequencing (LHC-BS) approach to examine the promoter methylome of HCCs, for which we customized 150,407 capture probes and enabled coverage of 91.8% of the RefSeq gene promoters within the human genome. We found the differential promoter DNA methylation between HCCs and peripheral normal tissues. Then we integrated promoter methylomic and transcriptomic profiling and described gene expression and regulation in HCCs. Lastly, we validated the key genes in a larger number of samples and screened candidate genes aberrantly regulated by DNA methylation in human HCCs. Capture-based whole genome promoter bisulfite-seq for 8 pairs of HCC tumor and non-tumor liver (NTL) samples.

2014-07-01 | E-GEOD-55752 | biostudies-arrayexpress

Dramatic effects of social behavior on gene regulation in rhesus macaques [Bisulfite seq]

Project description:These data are a component of a larger study investigating differences in gene regulation in relationship to rhesus macaque dominance rank. These data compare DNA methylation levels between individuals of different rank on a genome-wide scale using bisulfite sequencing DNA from peripheral blood mononuclear cells sampled from 3 high ranking individuals and 3 low ranking individuals (all adult female rhesus macaques)

2012-02-01 | E-GEOD-34128 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data