E-GEOD-56430
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PRJNA243294
PROVIDER: E-GEOD-56430 | ExpressionAtlas | 2015-08-04
REPOSITORIES: ExpressionAtlas
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| E-GEOD-56430-analysis-methods.tsv | Tabular | |||
| E-GEOD-56430-atlasExperimentSummary.Rdata | Rdata | |||
| E-GEOD-56430-configuration.xml | Xml | |||
| E-GEOD-56430-percentile-ranks.tsv | Tabular | |||
| E-GEOD-56430.condensed-sdrf.tsv | Tabular |
Items per page: 5 1 - 5 of 44 |
Similar Datasets
Project description:HIC2 is a novel dosage-dependent regulator of cardiac development within the distal 22q11 deletion syndrome region
| PRJNA243294 | ENA
Project description:Rationale: 22q11 deletion syndrome arises from recombination between low copy repeats on chromosome 22. Typical deletions result in hemizygosity for TBX1 associated with congenital cardiovascular disease. Deletions distal to the typically deleted region result in a similar cardiac phenotype but lack extra-cardiac features of the syndrome suggesting that a second haploinsufficient gene maps to this interval. Objective: The transcription factor HIC2 is lost in most distal deletions as well as a minority of typical deletions. We used mouse models to test the hypothesis that HIC2 hemizygosity causes congenital heart disease. Methods and Results: We created a genetrap mouse allele of Hic2. The genetrap reporter was expressed in the heart throughout the key stages of cardiac morphogenesis. Homozygosity for the genetrap allele was embryonic lethal before embryonic day E10.5 while the heterozygous condition exhibited a partially penetrant late lethality. One third of heterozygous embryos had a cardiac phenotype. Magnetic resonance imaging demonstrated a ventricular septal defect with overriding aorta. Conditional targeting indicated a requirement for Hic2 within the Nkx2.5+ and Mesp1+ cardiovascular progenitor lineages but not in the Wnt1+ neural crest or Mef2c+ second heart field lineages. Microarray analysis revealed increased expression of BMP10. Conclusions: Our results demonstrate a novel role for Hic2 in cardiac development. Hic2 is the first gene within the distal 22q11 interval to have a demonstrated haploinsufficient cardiac phenotype in mice. Together our data suggests HIC2 haploinsufficiency likely contributes to the cardiac defects seen in distal 22q11 deletion syndrome. The aim of this microarray experiment was to compare gene expression changes in the E13.5 mouse heart in a conditional knockout of Hic2 (Mesp1Cre/+; Hic2FL/FL) against control. All samples represent pools of isolated hearts from E13.5 mouse embryos. 3 replicates of each genotype were assayed. The genotypes are: 'WT' (Hic2FL/FL) 'KO' (Mesp1Cre/+; Hic2 FL/FL)
2014-04-02 | E-GEOD-56430 | biostudies-arrayexpress
Project description:Rationale: 22q11 deletion syndrome arises from recombination between low copy repeats on chromosome 22. Typical deletions result in hemizygosity for TBX1 associated with congenital cardiovascular disease. Deletions distal to the typically deleted region result in a similar cardiac phenotype but lack extra-cardiac features of the syndrome suggesting that a second haploinsufficient gene maps to this interval. Objective: The transcription factor HIC2 is lost in most distal deletions as well as a minority of typical deletions. We used mouse models to test the hypothesis that HIC2 hemizygosity causes congenital heart disease. Methods and Results: We created a genetrap mouse allele of Hic2. The genetrap reporter was expressed in the heart throughout the key stages of cardiac morphogenesis. Homozygosity for the genetrap allele was embryonic lethal before embryonic day E10.5 while the heterozygous condition exhibited a partially penetrant late lethality. One third of heterozygous embryos had a cardiac phenotype. Magnetic resonance imaging demonstrated a ventricular septal defect with overriding aorta. Conditional targeting indicated a requirement for Hic2 within the Nkx2.5+ and Mesp1+ cardiovascular progenitor lineages but not in the Wnt1+ neural crest or Mef2c+ second heart field lineages. Microarray analysis revealed increased expression of BMP10. Conclusions: Our results demonstrate a novel role for Hic2 in cardiac development. Hic2 is the first gene within the distal 22q11 interval to have a demonstrated haploinsufficient cardiac phenotype in mice. Together our data suggests HIC2 haploinsufficiency likely contributes to the cardiac defects seen in distal 22q11 deletion syndrome. the aim of this microarray experiment was to compare gene expression changes in the E13.5 mouse heart in a conditional knockout of Hic2 (Mesp1Cre/+; Hic2FL/FL) against control.
2014-04-02 | GSE56430 | GEO
Project description:B-cell development is dependent on the coordinated expression and cooperation of several transcription factors. Here, we show that the transcription factor ETS Related Gene (ERG) is crucial for normal B-cell development, and that its deletion results in a substantial loss of bone marrow B-cell progenitors and peripheral B-cells as well as a skewing of splenic B-cell populations. We found that ERG-deficient B-lineage cells exhibited an early developmental block, at the pre-B cell stage, and proliferated less. The cells failed to express the immunoglobulin heavy chain due to inefficient V-to-DJ recombination and cells that managed to undergo recombination displayed a strong bias against incorporation of distal V gene segments. Furthermore, antisense transcription at PAX5-activated intergenic repeat (PAIR) elements located in the distal region of the Igh locus was completely dependent on ERG. These findings identify ERG as a novel critical regulator of B-cell development by ensuring efficient and balanced V-to-DJ recombination.
2019-11-24 | GSE128977 | GEO
Project description:B-cell development is dependent on the coordinated expression and cooperation of several transcription factors. Here, we show that the transcription factor ETS Related Gene (ERG) is crucial for normal B-cell development, and that its deletion results in a substantial loss of bone marrow B-cell progenitors and peripheral B-cells as well as a skewing of splenic B-cell populations. We found that ERG-deficient B-lineage cells exhibited an early developmental block, at the pre-B cell stage, and proliferated less. The cells failed to express the immunoglobulin heavy chain due to inefficient V-to-DJ recombination and cells that managed to undergo recombination displayed a strong bias against incorporation of distal V gene segments. Furthermore, antisense transcription at PAX5-activated intergenic repeat (PAIR) elements located in the distal region of the Igh locus was completely dependent on ERG. These findings identify ERG as a novel critical regulator of B-cell development by ensuring efficient and balanced V-to-DJ recombination.
2019-11-24 | GSE128976 | GEO
Project description:B-cell development is dependent on the coordinated expression and cooperation of several transcription factors. Here, we show that the transcription factor ETS Related Gene (ERG) is crucial for normal B-cell development, and that its deletion results in a substantial loss of bone marrow B-cell progenitors and peripheral B-cells as well as a skewing of splenic B-cell populations. We found that ERG-deficient B-lineage cells exhibited an early developmental block, at the pre-B cell stage, and proliferated less. The cells failed to express the immunoglobulin heavy chain due to inefficient V-to-DJ recombination and cells that managed to undergo recombination displayed a strong bias against incorporation of distal V gene segments. Furthermore, antisense transcription at PAX5-activated intergenic repeat (PAIR) elements located in the distal region of the Igh locus was completely dependent on ERG. These findings identify ERG as a novel critical regulator of B-cell development by ensuring efficient and balanced V-to-DJ recombination.
2019-11-24 | GSE128975 | GEO
Project description:Loss of the PR domain 16 (PRDM16) genetic locus has been suggested as the needed trigger for the development of left ventricular non-compaction cardiomyopathy (LVNC) and dilated cardiomyopathy (DCM) in patients with 1p36 deletion syndrome. Furthermore, lack of Prdm16 in the murine heart has recently been shown to cause a spectrum of cardiomyopathy phenotypes. In spite of these advances, our understanding of the downstream transcriptional pathways regulated by PRDM16 that lead to these cardiac phenotypes is limited. OBJECTIVE: to unveil the downstream transcriptional pathways involved in the development of cardiomyopathy phenotypes associated with PRDM16 mutations/deletion in human and mice. METHODS AND RESULTS: We hypothesized that PRDM16 acts as an upstream regulator of key transcriptional pathways involved in cardiac maturation. Induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a patient with a PRDM16 variant, cardiac tissue from mice expressing the human variant, mice with cardiac-specific deletion of Prdm16 and in vitro gain and loss of Prdm16 function were employed. Here we show that de novo pathogenic variants in PRDM16 are sufficient to cause LVNC in humans. In contrast, haploinsufficiency or complete deletion of Prdm16 in cardiomyocytes in mice led to pathological hypertrophy and dilated cardiomyopathy respectively. We demonstrated that PRDM16 regulates cardiac maturation through the maintenance of estrogen-related receptors (ERRs) expression. By contrast, PRDM16 acts as a supressor of transforming growth factor beta (TGFB) signaling. CONCLUSIONS: PRDM16 is a novel regulator of cardiac maturation acting upstream of ERRs and their regulators, and a suppressor of fibrotic signaling including TGFB.
2023-12-01 | GSE193873 | GEO
Project description:Loss of the PR domain 16 (PRDM16) genetic locus has been suggested as the needed trigger for the development of left ventricular non-compaction cardiomyopathy (LVNC) and dilated cardiomyopathy (DCM) in patients with 1p36 deletion syndrome. Furthermore, lack of Prdm16 in the murine heart has recently been shown to cause a spectrum of cardiomyopathy phenotypes. In spite of these advances, our understanding of the downstream transcriptional pathways regulated by PRDM16 that lead to these cardiac phenotypes is limited. OBJECTIVE: to unveil the downstream transcriptional pathways involved in the development of cardiomyopathy phenotypes associated with PRDM16 mutations/deletion in human and mice. METHODS AND RESULTS: We hypothesized that PRDM16 acts as an upstream regulator of key transcriptional pathways involved in cardiac maturation. Induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a patient with a PRDM16 variant, cardiac tissue from mice expressing the human variant, mice with cardiac-specific deletion of Prdm16 and in vitro gain and loss of Prdm16 function were employed. Here we show that de novo pathogenic variants in PRDM16 are sufficient to cause LVNC in humans. In contrast, haploinsufficiency or complete deletion of Prdm16 in cardiomyocytes in mice led to pathological hypertrophy and dilated cardiomyopathy respectively. We demonstrated that PRDM16 regulates cardiac maturation through the maintenance of estrogen-related receptors (ERRs) expression. By contrast, PRDM16 acts as a supressor of transforming growth factor beta (TGFB) signaling. CONCLUSIONS: PRDM16 is a novel regulator of cardiac maturation acting upstream of ERRs and their regulators, and a suppressor of fibrotic signaling including TGFB.
2023-12-01 | GSE193877 | GEO
Project description:We report the effect on genome-wide gene expression after deletion of an enhancer region downstream of Sox2 in F1 ES cells. The Sox2 transcription factor must be robustly transcribed in embryonic stem (ES) cells to maintain pluripotency. Reporter assays reveal novel enhancers, including two enhancers over 100 kb downstream (SRR107 and SRR111) which, through the formation of chromatin loops, localise to the Sox2 promoter in ES cells. Using CRISPR/Cas9 we deleted a region containing these two enhancers, which we term the Sox2 control region (SCR). This deletion revealed that the SCR is required for Sox2 transcription in ES cells. Furthermore, homozygous deletion of this distal Sox2 control region (SCR) caused significant reduction in Sox2 mRNA and protein levels, loss of ES cell colony morphology, genome-wide changes in gene expression and impaired neuroectodermal formation upon spontaneous differentiation to embryoid bodies. Together these data identify a distal control region essential for Sox2 transcription in ES cells. Examination of PolA+ RNA after heterozygous and homozygous enhancer deletion in F1 ES cells (M. musculus129 x M. castaneus).
2014-11-19 | E-GEOD-58339 | biostudies-arrayexpress
Project description:To identify a functional gene regulatory network that orchestrate transcriptional programs to direct proper outflow tract development, we generated transgenic mice harboring a 226bp-deletion within a GATA-dependent, highly conserved cardiac enhancer region. We then performed gene expression profiling analysis using data obtained from RNA-seq of outflow tract in wildtype and homozygous mutant littermates at embryonic day 12.5.
2023-10-04 | GSE227361 | GEO