Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

47 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcription profiling by array of the Ts(1716)65Dn Down syndrome mouse model bone marrow lineage- c-Kit+ Sca-1+ (LSK), CMP, GMP and MEP progenitor cell populations, in which trisomy of Erg was specifically reduced to disomy using the Mld2 allele

ABSTRACT: Down syndrome (DS), with trisomy of chromosome 21 (HSA21), is the commonest human aneuploidy. Pre-leukemic myeloproliferative changes in DS fetal livers precedes the acquisition of GATA1 mutations, transient myeloproliferative disorder (DS-TMD) and acute megakaryocytic leukemia (DS-AMKL). Trisomy of the Erg gene is required for myeloproliferation in the Ts(1716)65Dn DS mouse model. We demonstrate here that genetic changes due trisomy of Erg lead to lineage priming of primitive and early multipotential progenitor cells in Ts(1716)65Dn mice, excess megakaryocyte-erythroid progenitors, and malignant myeloproliferation. Correlation of gene expression changes caused by Erg trisomy in Ts(1716)65Dn multilineage progenitor cells with those associated with trisomy 21 in human DS HSCs support a role for ERG as a regulator of hematopoietic lineage potential, trisomy of which drives pre-leukemic changes in DS fetal livers that predispose to subsequent DS-TMD and DS-AMKL.

INSTRUMENT(S): MouseWG-6_V2_0_R1_11278593_A

ORGANISM(S): Mus musculus

SUBMITTER: Ashley Ng

PROVIDER: E-MTAB-2574 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Epigenetic changes in Down syndrome leukemogenesis

Project description:Acute megakaryoblastic leukemia (AMKL) is more frequently seen in Down syndrome patients, where it is often preceded by a transient myeloproliferative disorder (DS-TMD). The development of DS-TMD and DS-AMKL require not only the presence of the trisomy 21 but also that of GATA1 mutations. However, despite extensive studies into the genetics of DS-AMKL, not much is known about the epigenetic deregulation associated with this disease. In order to understand how epigenetic changes at the DNA methylation level contribute to DS leukemogenesis we performed DNA methylation profiling at different stages of development of this disease and analyzed the dynamics of epigenetic reprogramming. Early genome-wide epigenetic changes can be detected in trisomy 21 fetal liver mononuclear cells, even prior to the development of hematological abnormalities. These early changes are characterized by marked loss of DNA methylation at genes associated with regulation of key developmental processes. This first wave of aberrant DNA hypomethylation is followed by a second wave of epigenetic reprogramming detected in blast cells from DS-TMD and DS-AMKL, characterized by gains of methylation. This second wave of hypermethylation targets a distinct set of genes, preferentially affecting genes involved in hematopoiesis and regulation of cell growth and proliferation. DNA methylation profiles obtained at different stages of the development of Down syndrome AMKL and from CD41+ cells from partial trisomic mice

2013-08-19 | E-GEOD-46167 | biostudies-arrayexpress

Epigenetic changes in Down syndrome leukemogenesis

2013-08-19 | GSE46167 | GEO

Expression data from transgenic ERG, GATA1s KI and ERG/GATA1s fetal livers

Project description:DS children have a 500-fold increased risk for developing acute megakaryoblastic leukemia (AMKL). Around 10% of DS newborns have a transient myeloproliferative disorder (TMD) that resolves spontaneously. Somatic mutations acquired during fetal hematopoiesis in the GATA1 transcription factor are detected in megakaryoblasts from all the DS TMDs or AMKLs. GATA1 is an X chromosome transcription factor essential for the development of multiple hematopoietic lineages. Loss of GATA1 results in embryonic lethality due to severe anemia. The GATA1 mutations result in the expression of a shorter isoform, GATA1s. Replacement of GATA1 with GATA1s causes transient proliferation of immature fetal megakaryocytic progenitors. The Hsa21 ETS transcription factor, ERG, is expressed in megakaryocytes and erythrocytes and is involved in several types of cancer. Mutation in GATA1 gene leading to expression of the short isoform (GATA1s) that occurs on the background of trisomy 21 is regarded as one of the driving forces for megakaryocytic expansion observed in DS fetal livers. ERG, which is located on chromosome 21, is considered one of the leading candidates to cooperate with GATA1 mutation in the generation of DS AMKL. To study the in vivo cooperation between ERG and GATA1 isoforms, we crossed the ERG transgenic mice with the GATA1s Knock-in mice (GATA null background). We found that males expressing both ERG and the short isoform of GATA1(GATA1s) died in uterus between embryonic days E121/2 and E141/2.We studied erythropoiesis and megakaryopoiesis in fetal livers from the different genotypes generated from our cross. We used expression array to study the specific interaction of ERG with the different GATA1 isoforms in fetal livers from E121/2 and E141/2 and identify ERG, GATA1 and GATA1s target genes by comparing sets of genes that are activated or repressed in the presence of ERG and the two isoforms of GATA1.

2013-12-31 | E-GEOD-46481 | biostudies-arrayexpress

Expression data from transgenic ERG, GATA1s KI and ERG/GATA1s fetal livers

2013-12-31 | GSE46481 | GEO

Expression analysis of GATA1s murine megakaryocyte progenitors from bone marrow and fetal Liver

Project description:About 10% of Down syndrome (DS) infants are born with a myeloproliferative disorder (DS-TMD) that spontaneously resolves within the first few months of life. About 20-30% of these infants subsequently develop acute megakaryoblastic leukemia (DS-AMKL). In order to understand differences that may exist between fetal and bone marrow megakaryocyte progenitor cell populations we flow sorted megakaryocyte progenitor cells and performed microarray expression analysis. kewywords: Mouse megakaryocyte progenitors

2013-03-29 | GSE45619 | GEO

Expression analysis of BL6 murine megakaryocyte progenitors from bone marrow and fetal Liver

2013-03-29 | GSE45618 | GEO

Expression analysis of GATA1s murine megakaryocyte progenitors from bone marrow and fetal Liver

2013-03-29 | E-GEOD-45619 | biostudies-arrayexpress

Expression analysis of BL6 murine megakaryocyte progenitors from bone marrow and fetal Liver

2013-03-29 | E-GEOD-45618 | biostudies-arrayexpress

ATACseq : role of trisomy 21, GATAs mutation and associated mutations in the development of trisomy 21

Project description:Acute megakaryoblastic leukemia of Down syndrome (DS-AMKL) is a model of clonal evolution from a preleukemic transient myeloproliferative disorder requiring both a trisomy 21 (T21) and a GATA1s mutation to a leukemia driven by additional driver mutations. We modelled this leukemic evolution through stepwise gene editing of GATA1s, SMC3+/- and MPLW515K providing 20 different trisomy or disomy 21 iPSC clones. The CD41+/CD42+ MK were sorted (10 000 to 30 000 cells) and submitted to cell lysis, transposition, and purification steps. The transposed DNA fragments were amplified by PCR 12 times using adapters from the Nextera Index Kit (Illumina). PCR purification was performed using MinElute PCR Purification Kit (Qiagen, 28004) to remove large fragments and remaining primers. Library quality was assessed using an Agilent 2100 Bioanalyzer (Agilent Technologies 5067-4626). Libraries were sequenced using NovaSeq-6000 sequencer (Illumina; 50 bp paired-end reads).

2022-06-15 | E-MTAB-11044 | biostudies-arrayexpress

Gene expression profiling of Down Syndrome (DS)-AMKL and non-DS AMKL samples

Project description:The goal of this study is to define a gene expression signature unique to DS-AMKL (acute megakaryoblastic leukemia or FAB M7 leukemia). A similar study was done previously, but using unfractionated patient leukemic samples. In this study, we sorted megakaryocytic leukemia blasts from patients and then compared their gene expression signatures to those from similarly sorted blasts from patients with non-DS AMKL. This allowed us to identify a gene expression signature more unique to DS-AMKL samples.

2010-08-01 | GSE16677 | GEO

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