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Homo sapiens
5 Downloadable Samples
IlluminaHiSeq2000
Description
Although many distinct mutations in a variety of genes are known to cause Amyotrophic Lateral Sclerosis (ALS), it remains poorly understood how they selectively impact motor neuron biology and whether they converge on common pathways to cause neural degeneration. Here, we have combined reprogramming and stem cell differentiation approaches with genome engineering and RNA sequencing to define the transcriptional changes that are induced in human motor neurons by mutant SOD1. Mutant SOD1 protein induced a transcriptional signature indicative of increased oxidative stress, reduced mitochondrial function, altered sub-cellular transport as well as activation of the ER stress and unfolded protein response pathways. Functional studies demonstrated that perturbations in these pathways were indeed the source of altered transcript levels. Overall design: 5 samples, 2 patient-derived SOD1A4V and 3 isogenic control samples where the mutation has been corrected. All samples are motor neurons derived from induced pluripotent stem cells (iPSCs), and isolated after lentiviral infection with an Hb9:RFP construct and FACS purification. Each sample is a separate biological replicate.
Publication Title
Pathways disrupted in human ALS motor neurons identified through genetic correction of mutant SOD1.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 14 Downloadable Samples
- NextSeq 500
Description
Diamond-Blackfan anemia (DBA) is a rare bone marrow failure disorder that affects 7 out of 1,000,000 live births and has been associated with mutations in components of the ribosome. In order to characterize the genetic landscape of this heterogeneous disorder, we recruited a cohort of 472 individuals with a clinical diagnosis of DBA and performed whole exome sequencing (WES). We identified rare and predicted damaging mutations in likely causal genes for 78% of individuals. The majority of mutations were singletons, absent from population databases, predicted to cause loss of function, and in one of 19 previously reported ribosomal protein (RP) encoding genes. Using exon coverage estimates, we identified and validated 31 deletions in RP genes. We also observed an enrichment for extended splice site mutations and validated their diverse effects using RNA sequencing in individual-derived cell lines. Leveraging the size of our cohort, we observed robust genotype-phenotype associations with congenital abnormalities and treatment outcomes. We further identified rare mutations in 7 previously unreported RP genes that may cause DBA, as well as several distinct disorders that appear to phenocopy DBA, including 9 individuals with biallelic CECR1 mutations that result in deficiency of ADA2. However, no new genes were identified at exome-wide significance, suggesting that there are no unidentified genes containing mutations readily identified by WES that explain > 5% of DBA cases. Overall, this report should not only inform clinical practice for DBA individuals, but also the design and analysis of rare variant studies for heterogeneous Mendelian disorders. Overall design: 9 individuals with DBA with putative splice mutations and 5 control individuals were processed for RNA-seq.
Publication Title
The Genetic Landscape of Diamond-Blackfan Anemia.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples
GSE22176- Homo sapiens
- 78 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution.
Sample Metadata Fields
Cell line, Time
View Samples- Homo sapiens
- 54 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Genome-wide expression analysis of hapmap lymphoblastoid and ENCODE project cell lines stimulated with calcitriol
Publication Title
A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution.
Sample Metadata Fields
Cell line, Time
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Genome-wide expression analysis of hapmap lymphoblastoid and ENCODE project cell lines stimulated with calcitriol and/or estrogen
Publication Title
A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution.
Sample Metadata Fields
Cell line, Time
View Samples- Mus musculus
- 32 Downloadable Samples
- Illumina HiSeq 2500, Illumina HiSeq 2000
Description
The juvenile onset of spermatogenesis in mice is analyzed by combining cytological and transcriptomic data in a novel computational analysis, resulting in meiotic substage-specific transcriptomes and the discovery of a transcription factor network that regulates the substages of meiosis. Overall design: Germ cells from testes of individual mice were obtained at two-day intervals from 8 to 18 days post-partum (dpp), with five biological replicates at each age (samples 8_1 through 18_5). Eight stages were discriminated cytologically by combinatorial antibody labeling, and RNA-seq was performed on the same samples. A novel permutation-based maximum covariance analysis (PMCA) method was developed to deconvolve genes into meiotic substages. To verify PMCA derived pachytene/diplotene substage-specific genes, we isolated enriched populations of adult pachytene germ cells (samples rep1 through rep4), followed the same RNA-seq protocol, and compared the PMCA derived substage-specific gene lists to the genes expressed in the pachytene/diplotene enriched germ cells.
Publication Title
Regulatory complexity revealed by integrated cytological and RNA-seq analyses of meiotic substages in mouse spermatocytes.
Sample Metadata Fields
Sex, Age, Cell line, Subject
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina Genome Analyzer II, Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptional network analysis in muscle reveals AP-1 as a partner of PGC-1α in the regulation of the hypoxic gene program.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 7 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st), Illumina Genome Analyzer II
Description
Skeletal muscle tissue shows an extraordinary cellular plasticity, but the underlying molecular mechanisms are still poorly understood. Here we use a combination of experimental and computational approaches to unravel the complex transcriptional network of muscle cell plasticity centered on the peroxisome proliferator-activated receptor coactivator 1 (PGC-1), a regulatory nexus in endurance training adaptation. By integrating data on genome-wide binding of PGC-1 and gene expression upon PGC-1 over-expression with comprehensive computational prediction of transcription factor binding sites (TFBSs), we uncover a hitherto underestimated number of transcription factor partners involved in mediating PGC-1 action. In particular, principal component analysis of TFBSs at PGC-1 binding regions predicts that, besides the well-known role of the estrogen-related receptor (ERR), the activator protein-1 complex (AP-1) plays a major role in regulating the PGC-1-controlled gene program of hypoxia response. Our findings thus reveal the complex transcriptional network of muscle cell plasticity controlled by PGC-1.
Publication Title
Transcriptional network analysis in muscle reveals AP-1 as a partner of PGC-1α in the regulation of the hypoxic gene program.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The peroxisome proliferator-activated receptor co-activator 1 (PGC-1) coordinates the transcriptional network response to promote an improved endurance capacity in skeletal muscle, e.g. by co-activating the estrogen-related receptor (ERR) in the regulation of oxidative substrate metabolism. Despite a close functional relationship, the interaction between these two proteins has not been studied on a genomic level. We now mapped the genome-wide binding of ERR to DNA in skeletal muscle cell line with elevated PGC-1 and linked the DNA recruitment to global PGC-1 target gene regulation. We found that, surprisingly, ERR co-activation by PGC-1 is only observed in the minority of all PGC-1 recruitment sites. Nevertheless, a majority of PGC-1 target gene expression is dependent on ERR. Intriguingly, the interaction between these two proteins is controlled by the genomic context of response elements, in particular the relative GC and CpG content, monomeric and dimeric repeat binding site configuration for ERR, and adjacent recruitment of the transcription factor SP1. These findings thus not only reveal an unprecedented insight into the regulatory network underlying muscle cell plasticity, but also strongly link the genomic context of DNA response elements to control transcription factor - co-regulator interactions.
Publication Title
The Genomic Context and Corecruitment of SP1 Affect ERRα Coactivation by PGC-1α in Muscle Cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina Genome Analyzer II, Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Skeletal muscle tissue shows an extraordinary cellular plasticity, but the underlying molecular mechanisms are still poorly understood. Here we use a combination of experimental and computational approaches to unravel the complex transcriptional network of muscle cell plasticity centered on the peroxisome proliferator-activated receptor coactivator 1 (PGC-1), a regulatory nexus in endurance training adaptation. By integrating data on genome-wide binding of PGC-1 and gene expression upon PGC-1 over-expression with comprehensive computational prediction of transcription factor binding sites (TFBSs), we uncover a hitherto underestimated number of transcription factor partners involved in mediating PGC-1 action. In particular, principal component analysis of TFBSs at PGC-1 binding regions predicts that, besides the well-known role of the estrogen-related receptor (ERR), the activator protein-1 complex (AP-1) plays a major role in regulating the PGC-1-controlled gene program of hypoxia response. Our findings thus reveal the complex transcriptional network of muscle cell plasticity controlled by PGC-1.
Publication Title
Transcriptional network analysis in muscle reveals AP-1 as a partner of PGC-1α in the regulation of the hypoxic gene program.
Sample Metadata Fields
No sample metadata fields
View Samples