Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A mouse Embryonic Stem Cell Bank for inducible overexpression of human chromosome 21 genes

ABSTRACT: The HSA21-mES Cell Bank includes, in triplicate clones, thirty-two murine orthologs of HSA21 genes, which can be overexpressed in an inducible manner using the Tet-off system integrated in the Rosa26 locus. The following subset of twenty clones were characterized by microarray analysis: Bach1, Erg, Ets2, Gabpa, ZFP295, Nrip1, Olig1, Olig2, Pknox1, 1810007M14Rik, Runx1, Aire, Sim2, Dscr1, DYRK1A, SNF1LK, Ripk4 , Hunk, Pdxk, Pfkl. Each triplicate clone was transcriptionally profiled by microarray analysis using Affymetrix Mouse 430_2 arrays before and after induction (Affymetrix 430A_2 in case of Runx1), yielding six arrays for each overexpression experiment.

ORGANISM(S): Mus musculus

SUBMITTER: Mario Lauria

PROVIDER: E-GEOD-19836 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Publications

A mouse embryonic stem cell bank for inducible overexpression of human chromosome 21 genes.

De Cegli Rossella R Romito Antonio A Iacobacci Simona S Mao Lei L Lauria Mario M Fedele Anthony O AO Klose Joachim J Borel Christelle C Descombes Patrick P Antonarakis Stylianos E SE di Bernardo Diego D Banfi Sandro S Ballabio Andrea A Cobellis Gilda G

Genome biology 20100622 6

<h4>Background</h4>Dosage imbalance is responsible for several genetic diseases, among which Down syndrome is caused by the trisomy of human chromosome 21.<h4>Results</h4>To elucidate the extent to which the dosage imbalance of specific human chromosome 21 genes perturb distinct molecular pathways, we developed the first mouse embryonic stem (ES) cell bank of human chromosome 21 genes. The human chromosome 21-mouse ES cell bank includes, in triplicate clones, 32 human chromosome 21 genes, which ...[more]

PMID: 20569505

Similar Datasets

A mouse Embryonic Stem Cell Bank for inducible overexpression of human chromosome 21 genes

Project description:The HSA21-mES Cell Bank includes, in triplicate clones, thirty-two murine orthologs of HSA21 genes, which can be overexpressed in an inducible manner using the Tet-off system integrated in the Rosa26 locus. The following subset of twenty clones were characterized by microarray analysis: Bach1, Erg, Ets2, Gabpa, ZFP295, Nrip1, Olig1, Olig2, Pknox1, 1810007M14Rik, Runx1, Aire, Sim2, Dscr1, DYRK1A, SNF1LK, Ripk4 , Hunk, Pdxk, Pfkl.

2010-12-06 | GSE19836 | GEO

Augmented hematopoiesis in induced pluripotent stem cells derived from patients with Down syndrome.

Project description:To identify the genes, which led to the augmented hematopoiesis in DS-iPS cells, we performed gene expression profiling of D12-DS-iPS cells (DS-iPS-T32, DS-iPS-T33 and DS-iPS-T31) and control hiPS cells (253G1, 253G4 and A31) generated by 3 factors. In the comparison of gene expression levels in each DS-iPS cell clone with the average of these in control iPS cell clones, 972 genes showed more than 2-fold increased expression, and 1118 genes showed decreased expression in all DS-iPS cell clones. Among these upregulated genes, 61 genes including GATA1 were involved in hematopoiesis-related genes according to Ingenuity Pathways Analysis (IPA). Among the above 2-fold more upregulated genes in DS-iPS cells, 18 genes were on Hsa21. The expression of RUNX1 on Hsa21, a hematopoiesis-related gene, was significantly upregulated in DS-iPS cells. The high expressions of GATA1 and RUNX1 were also identified in 4-factor DS-iPS cells.

2011-11-29 | GSE33911 | GEO

RUNX1 isoforms in leukemogenesis

Project description:Aneuploidy and structural aberrations affecting chromosome 21 (Hsa21) are the most frequent in cytogentic events in acute myeloid leukemia. However, it remains unclear why leukemic blasts select for amplifications of Hsa21 or parts of it and why children with Down syndrome (i.e. trisomy 21) are at a high risk of developing leukemia. Here, we propose that disequilibrium of the RUNX1 isoforms and resultant RUNX1A dominance are key to trisomy 21-associated leukemogenesis. Using a Hsa21-focussed CRISPR-Cas9 screen, we uncovered a strong and specific RUNX1 dependency in myeloid leukemia associated with Down syndrome (ML-DS). High levels of RUNX1A – as seen in ML-DS – synergized with the pathognomonic Gata1s mutation in ML-DS pathogenesis, an effect that was reversed upon restoration of the normal RUNX1A:RUNX1C equilibrium. Mechanistically, RUNX1A displaces RUNX1C from its endogenous binding sites and recruits the MYC cofactor MAX to induce oncogenic programs and perturb normal differentiation. This presents a therapeutic vulnerability that can be exploited by interfering with MYC:MAX dimerization. Our study highlights the importance of alternative splicing in leukemogenesis, and paves the way for developing specific and targeted therapies for ML-DS as well as for other leukemias with Hsa21 aneuploidy or RUNX1 isoform disequilibrium.

2023-05-10 | PXD030616 | Pride

Augmented hematopoiesis in induced pluripotent stem cells derived from patients with Down syndrome.

2011-11-29 | E-GEOD-33911 | biostudies-arrayexpress

Synergistic roles of DYRK1A and GATA1 in trisomy 21 megakaryopoiesis

Project description:Patients with Down syndrome (DS, trisomy 21, T21) are at increased risk of transient abnormal myelopoiesis (TAM) and acute megakaryoblastic leukemia (ML-DS). Both TAM and ML-DS require prenatal somatic mutations in GATA1, resulting in the truncated isoform GATA1s. The mechanism by which individual chromosome 21 (HSA21) genes synergize with GATA1s for leukemic transformation is challenging to study, in part due to limited human cell models with wild type GATA1 or GATA1s. HSA21-encoded DYRK1A is overexpressed in ML-DS and may be a therapeutic target. To determine how DYRK1A influences hematopoiesis in concert with GATA1s, we used gene editing to disrupt all 3 alleles of DYRK1A in isogenic T21 induced pluripotent stem cells (iPSCs) with and without the GATA1s mutation. Unexpectedly, hematopoietic differentiation revealed that DYRK1A loss combined with GATA1s leads to increased megakaryocyte proliferation and decreased maturation. This proliferative phenotype was associated with upregulation of D-type cyclins and hyperphosphorylation of Rb to allow E2F release and de-repression of its downstream targets. Notably, DYRK1A loss had no effect in T21/wtGATA1 megakaryocytes. These surprising results suggest that increased DYRK1A expression may be protective against TAM and ML-DS and that DYRK1A inhibition would not be a therapeutic option for GATA1s-associated leukemias.

2023-11-04 | GSE243702 | GEO

Correction of cognitive deficits in mouse models of Down syndrome by pharmacological inhibitor of DYRK1A

Project description:Down Syndrome (DS) results from the trisomy of human chromosome 21 (HSA21). It is still the most frequent intellectual disability, affecting 1 newborn per 700 births. Among candidate genes explaining intellectual disabilities seen in DS patients, the dual specificity tyrosine-phosphorylation regulated kinase 1A, DYRK1A, is located in the DS critical region of chromosome 21. DYRK1A has become a major screening target for the development of selective and potent pharmacological inhibitors. We here investigated the effects of a relatively selective DYRK1A inhibitor, Leucettine 41 (hereafter L41) in three different trisomic mouse models with increasing genetic complexity, Tg(Dyrk1a), Ts65Dn and Dp1Yey. Leucettines are derived from the marine sponge alkaloid Leucettamine B.

2018-10-17 | PXD008419 | Pride

Discovery of DYRK1A dependent phosphorylation in mouse embryonic heart

Project description:The Dp1Tyb mouse model for Down syndrome contains a duplication of 23Mb of mouse chromosome 16 (Mmu16) that is orthologous to human chromosome 21 (Hsa21). This region contains 145 coding genes, and thus these genes are present in 3 copies. Dp1Tyb mice display congenital heart defects, similar to the ones seen in people with Down syndrome. These defects include ventricular and atrio-ventricular septal defects and are seen at embryonic day 14.5 (E14.5) of gestation. One of the 145 genes present in 3 copies in Dp1Tyb mice codes for a kinase called DYRK1A. We found that by crossing Dp1Tyb mice with mice carrying a heterozygous Dyrk1a loss of function allele, thereby reducing the dosage of the Dyrk1a gene from 3 to 2 copies, we rescue the congenital heart defects. Thus 3 copies of Dyrk1a are required to cause heart defects, and, presumably, increased DYRK1A protein is required for the heart defects. We compared the phosphoproteome in Dp1Tyb versus Dp1TybDyrk1a+/+/- embryonic hearts in order to discover alterations in phosphoproteins that could pinpoint molecular mechanisms that give rise to the congenital heart defects. The two strains (Dp1Tyb and Dp1TybDyrk1a+/+/-) differ only in the copy number of Dyrk1a (3 v 2) and thus differences in phosphoproteins would include both direct and indirect targets of DYRK1A activity.

2024-02-01 | PXD013053 | Pride

Dyrk1a dosage effects on the transcriptome of embryonic hearts from the Dp1Tyb mouse model of Down syndrome using bulk RNAseq

Project description:We performed bulk RNAseq on whole hearts from E13.5 Dp1Tyb embryos and from wild-type littermates, as well as hearts from E13.5 Dp1TybDyrk1a+/+/- embryos and wild-type littermates. Analysis showed the expected increased expression of the Hsa21-orthologous genes on Mmu16 that are present in 3 copies. Gene set enrichment analysis identified pathways that are altered in Dp1Tyb hearts. Some of these changes were dependent on 3 copies of Dyrk1a.

2024-01-25 | GSE196445 | GEO

Transcription profiling of expressed human chromosome 21 genes in transchromosomic mouse embryos carrying a freely segregating copy of Hsa21

Project description:Detection of expressed human chromosome 21 genes in transchromosomic mouse embryos carrying a freely segregating copy of Hsa21.

2005-11-19 | E-MEXP-409 | biostudies-arrayexpress

Chr21 protein-protein interactions: enrichment in proteins involved in intellectual disability, autism and late-onset Alzheimer’s disease

Project description:Down syndrome (DS) is caused by human chromosome 21 (HSA21) trisomy. It is characterized by a poorly understood intellectual disability (ID). We studied two mouse models of DS, one with an extra copy of the Dyrk1A gene (189N3) and the other with an extra copy of the mouse Chr16 syntenic region (Dp(16)1Yey). RNA-seq analysis of the transcripts deregulated in the embryonic hippocampus revealed an enrichment in genes associated with chromatin for the 189N3 model and synapses for the Dp(16)1Yey model

2022-07-18 | GSE201290 | 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