Filters
Technology
Platform
GSE12408
Homo sapiens
39 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The Cohesin apparatus has a canonical role in sister chromatid cohesion. Heterozygous mutations in Nipped B-like (NIPBL), SMC1A, and SMC3 have been found in 60% of probands with Cornelia de Lange Syndrome (CdLS), a dominant multi-system genetic disorder with variable expression. We have performed a genome-wide transcription assessment as well as cohesin binding analysis using human lymphoblastoid cell lines (LCLs) from probands with CdLS and controls. Here, we report a unique profile of genes dysregulated in CdLS that correlates with different clinical presentations. Genome-wide analysis of cohesin binding demonstrates a preference for intergenic regions suggesting a cis-regulatory function mimicking that of an insulator. However, the binding sites are enriched within the promoter regions of the dysregulated genes and are significantly decreased in CdLS probands, indicating an alternative role of cohesin as a classic transcription factor. Cohesin also co-localizes with CTCF at the boundary elements affecting neighboring gene expression in CdLS probands. We propose that the CdLS phenotype is the result of dysregulated gene expression rather than defective sister chromatid cohesion. Phenotype specific expression profiles are also described.
Publication Title
Transcriptional dysregulation in NIPBL and cohesin mutant human cells.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Induced pluripotent stem cells hold great promise for modeling human hematopoietic diseases. However, intrinsic variability in the capacities of different iPSC lines for hematopoietic development complicates comparative studies and is currently unexplained.
Publication Title
Clonal genetic and hematopoietic heterogeneity among human-induced pluripotent stem cell lines.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
CHOPS syndrome is caused by germline gain-of-function mutations of AFF4. Cornelia de Lange syndrome is caused by germline mutations of cohesin loading factors or cohesin complex genes such as NIPBL, SMC1A, SMC3 and HDAC8. There are many overlapping clinical features exist between CHOPS syndrome and Cornelia de Lange syndrome. To identified commonly dysregulated genes in CHOPS syndrome and Cornelia de Lange syndrome, we perfomred side-by-side transcriptome comparison between CHOPS syndrome and Cornelia de Lange syndrome.
Publication Title
Germline gain-of-function mutations in AFF4 cause a developmental syndrome functionally linking the super elongation complex and cohesin.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Missense mutations in transcription factor GATA1 underlie several distinct forms of anemia and thrombocytopenia. Clinical severity depends on the site and type of substitution, and distinct substiutions of the same residue produce disparate phenotypes. To investigate the effect of GATA1 missense mutations on erythroid differentiation we expressed conditionally activated wild type or mutant versions of GATA1 in GATA1-null G1E cells.
Publication Title
Analysis of disease-causing GATA1 mutations in murine gene complementation systems.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Common Lymphoid Progenitors (CLPs) have two subsets, Ly-6d- which are mutli-potent, and Ly-6d, which derive from Ly-6d- and are committeed to the B-cell fate. Treatment of a mouse with CpG DNA causes an inflammatory response that alters both subsets. We used expression data to understand the changes in transcription in the transition of Ly-6d- CLPs to Ly-6d+ CLPs ion the presence and absence of CpG induced inflammation.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
AFF4 is a component of super elongation complex (SEC), which plays an important role in mobilizing paused RNA polymerase II at gene promoter regions. Using exome sequenging, we have identified a novel genetic disorder caused by missense mutations in AFF4. We propose CHOPS syndrome as a name for this new diagnosis. To evaluate the effect of identified missense mutations of AFF4, utilizing patient derived skin fibroblast cell lines, the gene expression analysis was perfomred.
Publication Title
Germline gain-of-function mutations in AFF4 cause a developmental syndrome functionally linking the super elongation complex and cohesin.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Intrahepatic biliary and arterial development proceed with complex orchestrations involving Notch, TgfB, Wnt and Vegf signaling within the portal tracts of the liver. These pathways
Publication Title
No associated publication
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
microRNA miR-144/451 is highly expressed during erythropoiesis. We deleted the miR-144/451 gene locus in mice and compared the transcriptomes of miR-144/451-null bone marrow erythroid precursors to stage-matched wild-type control cells.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The transcription co-factor FOG1 interacts with the chromatin remodeling complex NuRD to mediate gene activation and gene repression during hematopoiesis. We have generated mice with a targeted mutation in the endogenous Fog1 locus that results in an N-ternimal mutation in FOG1 that disrupts the interaction with NuRD.
Publication Title
Pleiotropic platelet defects in mice with disrupted FOG1-NuRD interaction.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Dyskeratosis congenita is a bone marrow failure syndrome characterized by the presence of short telomeres at presentation. The X-linked form is caused by mutations in the gene DKC1, encoding the protein dyskerin. Dyskerin is required for in the assembly and stability of telomerase and is also involved in ribosomal RNA (rRNA) processing where it converts specific uridines to pseudouridine. DC is thought to result from failure to maintain tissues, like blood, that are renewed by stem cell activity, suggesting induced pluripotent stem (iPS) cells from X-linked DC patients may provide information about the mechanisms involved. Here we show that in iPS cells with DKC1 mutations Q31E, A353V and L37 telomere maintenance is compromised with short telomere lengths and decreased telomerase activity. The degree to which telomere lengths are affected by expression of telomerase during reprograming, or with ectopic expression of wild type dyskerin varies, with recurrent mutation A353V showing the most severe effect on telomere maintenance. A353V cells but not Q31E or L37 cells, are refractory to correction by incorporation of a single copy of a wild type DKC1 cDNA into the AAVS1 safe harbor locus. None of the mutant cells show decreased pseudouridine levels in rRNA or defective rRNA processing. Finally transcriptome analysis of the iPS cells shows that WNT signaling is significantly decreased in all mutant cells, raising the possibility that defective WNT signaling may contribute to disease pathogenesis.
Publication Title
Impaired Telomere Maintenance and Decreased Canonical WNT Signaling but Normal Ribosome Biogenesis in Induced Pluripotent Stem Cells from X-Linked Dyskeratosis Congenita Patients.
Sample Metadata Fields
Specimen part
View Samples