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accession-icon GSE25673
Comparing Control and Schizophrenic hiPSC-derived Neurons
  • organism-icon Homo sapiens
  • sample-icon 24 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 1.0 ST Array (hugene10st)

Description

Schizophrenia is a debilitating neurological disorder for which no cure exists. Few defining characteristics of schizophrenic neurons have been identified and the molecular mechanisms responsible for schizophrenia are not well understood, in part due to the lack of patient material for study. Human induced pluripotent stem cells (hiPSCs) offer a new strategy for studying schizophrenia. We have created the first cell-based human model of a complex genetic psychiatric disease by generating hiPSCs from schizophrenic patients and subsequently differentiating these cells to hiPSC-derived neurons in vitro. Schizophrenic hiPSC-derived neurons showed diminished neuronal connectivity in conjunction with decreased neurite number, PSD95-protein levels and glutamate receptor expression. Gene expression profiles of schizophrenic hiPSC-derived neurons identified altered expression of many components of the cAMP and WNT signaling pathways. Key cellular and molecular elements of the schizophrenic phenotype were ameliorated following treatment of schizophrenic hiPSC-derived neurons with the antipsychotic loxapine.

Publication Title

Modelling schizophrenia using human induced pluripotent stem cells.

Sample Metadata Fields

Sex, Disease, Disease stage

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accession-icon GSE77634
Enhanced CLIP (eCLIP) enables robust and scalable transcriptome-wide discovery and characterization of RNA binding protein binding sites
  • organism-icon Homo sapiens
  • sample-icon 10 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500, Affymetrix Human Transcriptome Array 2.0 (hta20)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Robust transcriptome-wide discovery of RNA-binding protein binding sites with enhanced CLIP (eCLIP).

Sample Metadata Fields

Cell line

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accession-icon GSE77339
Enhanced CLIP (eCLIP) enables robust and scalable transcriptome-wide discovery and characterization of RNA binding protein binding sites [array]
  • organism-icon Homo sapiens
  • sample-icon 10 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500, Affymetrix Human Transcriptome Array 2.0 (hta20)

Description

RNA binding proteins (RBPs) play essential roles in cellular physiology by interacting with target RNAs. As defects in protein-RNA recognition lead to human disease, UV-crosslinking and immunoprecipitation (CLIP) of ribonuclear complexes followed by deep sequencing (-seq) is critical in constructing protein-RNA maps to expand our understanding of RBP function. However, current CLIP protocols are technically demanding and involve low complexity libraries that yield squandered sequencing of PCR duplicates and high experimental failure rates. To enable truly large-scale implementation of CLIP-seq, we have developed an enhanced CLIP methodology (eCLIP) that features a decrease of ~10 cycles of requisite amplification with a concomitant >60% decrease in discarded PCR duplicate reads, while maintaining the ability to identify RNA binding with single-nucleotide resolution. By simplifying the generation of paired IgG and size-matched input controls, eCLIP also dramatically improves specificity in discovery of authentic binding sites. To demonstrate that eCLIP enables large-scale and robust profiling of RBPs, 102 eCLIP experiments in biological duplicate for a diverse collection of 74 RBPs in HepG2 and K562 cells were completed (available at https://www.encodeproject.org). We establish that eCLIP is comparable in amplification and sample requirements to ChIP-seq, and enables integrative analysis of diverse RBPs to reveal factor-specific profiles, common artifacts for CLIP experiments and RNA-centric perspectives of RBP activity.

Publication Title

Robust transcriptome-wide discovery of RNA-binding protein binding sites with enhanced CLIP (eCLIP).

Sample Metadata Fields

Cell line

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accession-icon SRP087936
RNA binding protein CPEB1 remodels host and viral RNA landscapes [RNA-Seq]
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon

Description

In this study, we report that HCMV infection results in widespread alternative splicing (AS), shorter 3'-untranslated regions (3'UTRs) and polyA tail lengthening in host genes and CPEB1 depletion reverses infection-related post-transcriptional changes. Overall design: We performed RNA-seq for Mock (Non-targeting siRNA), human Cytomegalovirus (HCMV) with non-targeting siRNA, and CPEB1 siRNA treated human foreskin fibroblasts (HFFs). We also performed RNA-seq for lentivirus mediated GFP overexpression (OE) and CPEB1 overexpression human foreskin fibroblasts. Lastly, we performed TAIL-seq for Mock (Non-targeting siRNA), human Cytomegalovirus (HCMV) with non-targeting siRNA, and CPEB1 siRNA treated HFFs.

Publication Title

RNA-binding protein CPEB1 remodels host and viral RNA landscapes.

Sample Metadata Fields

No sample metadata fields

View Samples
accession-icon GSE86464
HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons
  • organism-icon Mus musculus, Homo sapiens
  • sample-icon 63 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Transcriptome Array 2.0 (hta20), Illumina HiSeq 2000

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System.

Sample Metadata Fields

Age, Specimen part, Disease, Cell line, Treatment

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accession-icon GSE86462
HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [hnRNPA2B1_Arrays_human_iPSC_MN_Stress]
  • organism-icon Homo sapiens
  • sample-icon 41 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Transcriptome Array 2.0 (hta20)

Description

HnRNPA2B1 encodes an RNA binding protein associated with neurodegenerative disorders. However, its function in the nervous system is unclear. Transcriptome-wide cross-linking and immunoprecipitation in mouse spinal cord discover UAGG motifs enriched within ~2,500 hnRNP A2/B1 binding sites and an unexpected role for hnRNP A2/B1 in alternative polyadenylation. Loss of hnRNP A2/B1 results in alternative splicing, including skipping of an exon in amyotrophic lateral sclerosis (ALS)-associated D-amino acid oxidase (DAO) that reduces D-serine metabolism. Inclusion of the DAO exon is also reduced in transgenic ALS mice models. ALS-associated hnRNP A2/B1 D290V mutant patient fibroblasts and motor neurons differentiated from induced pluripotent stem cells demonstrate gain-of-mutant-dependent splicing differences. Mutant motor neurons also exhibit increased hnRNP A2/B1 localization to cytoplasmic granules during stress, which are abrogated by a small molecule CA43. Our findings and cellular resource identify RNA networks affected in loss of normal and mutated hnRNP A2/B1 with broad relevance to neurodegeneration.

Publication Title

Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System.

Sample Metadata Fields

Specimen part, Disease, Treatment

View Samples
accession-icon GSE86223
HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [hnRNPA2B1_Arrays_human_iPSC_MN_ASO]
  • organism-icon Homo sapiens
  • sample-icon 22 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Transcriptome Array 2.0 (hta20)

Description

HnRNPA2B1 encodes an RNA binding protein associated with neurodegenerative disorders. However, its function in the nervous system is unclear. Transcriptome-wide cross-linking and immunoprecipitation in mouse spinal cord discover UAGG motifs enriched within ~2,500 hnRNP A2/B1 binding sites and an unexpected role for hnRNP A2/B1 in alternative polyadenylation. Loss of hnRNP A2/B1 results in alternative splicing, including skipping of an exon in amyotrophic lateral sclerosis (ALS)-associated D-amino acid oxidase (DAO) that reduces D-serine metabolism. Inclusion of the DAO exon is also reduced in transgenic ALS mice models. ALS-associated hnRNP A2/B1 D290V mutant patient fibroblasts and motor neurons differentiated from induced pluripotent stem cells demonstrate gain-of-mutant-dependent splicing differences. Mutant motor neurons also exhibit increased hnRNP A2/B1 localization to cytoplasmic granules during stress, which are abrogated by a small molecule CA43. Our findings and cellular resource identify RNA networks affected in loss of normal and mutated hnRNP A2/B1 with broad relevance to neurodegeneration.

Publication Title

Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System.

Sample Metadata Fields

Specimen part, Disease, Treatment

View Samples
accession-icon SRP086702
HNRNPA2B1 regulates alternative RNA processing in the nervous system and accumulates in granules in ALS IPSC-derived motor neurons [hnRNPA2B1_RNA-seq_mouse_SC]
  • organism-icon Mus musculus
  • sample-icon 7 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000

Description

HnRNPA2B1 encodes an RNA binding protein associated with neurodegenerative disorders. However, its function in the nervous system is unclear. Transcriptome-wide cross-linking and immunoprecipitation in mouse spinal cord discover UAGG motifs enriched within ~2,500 hnRNP A2/B1 binding sites and an unexpected role for hnRNP A2/B1 in alternative polyadenylation. Loss of hnRNP A2/B1 results in alternative splicing, including skipping of an exon in amyotrophic lateral sclerosis (ALS)-associated D-amino acid oxidase (DAO) that reduces D-serine metabolism. Inclusion of the DAO exon is also reduced in transgenic ALS mice models. ALS-associated hnRNP A2/B1 D290V mutant patient fibroblasts and motor neurons differentiated from induced pluripotent stem cells demonstrate gain-of-mutant-dependent splicing differences. Mutant motor neurons also exhibit increased hnRNP A2/B1 localization to cytoplasmic granules during stress, which are abrogated by a small molecule CA43. Our findings and cellular resource identify RNA networks affected in loss of normal and mutated hnRNP A2/B1 with broad relevance to neurodegeneration. Overall design: RNA-seq in mouse spinal after injection with ASO against hnRNP A2/B1 or saline. Three or four replicates per condition

Publication Title

Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System.

Sample Metadata Fields

Specimen part, Cell line, Treatment, Subject

View Samples
accession-icon GSE16391
GGI: a potential predictor of relapse for endocrine-treated breast cancer patients in the BIG 1-98 trial
  • organism-icon Homo sapiens
  • sample-icon 53 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Background: We have previously shown that the Gene expression Grade Index (GGI) was able to identify two subtypes of estrogen receptor (ER)-positive tumors that were associated with statistically distinct clinical outcomes in both untreated and tamoxifen-treated patients. Here, we aim to investigate the ability of the GGI to predict relapses in postmenopausal women who were treated with tamoxifen (T) or letrozole (L) within the BIG 1-98 trial.

Publication Title

The Gene expression Grade Index: a potential predictor of relapse for endocrine-treated breast cancer patients in the BIG 1-98 trial.

Sample Metadata Fields

Age, Specimen part, Disease stage, Treatment

View Samples
accession-icon SRP198810
Stem cell-derived cranial and spinal motor neurons reveal proteostatic differences between ALS resistant and sensitive motor neurons
  • organism-icon Mus musculus
  • sample-icon 570 Downloadable Samples
  • Technology Badge IconNextSeq 500

Description

We report the comparative gene expression between embryonic stem cell derived cranial and spinal motor neurons and multiple time points after induction and primary cultured ocular and spinal motor neurons, using single cell RNA sequencing. Overall design: Single neurons were isolated in 96-well plates and their gene expression profiled using SMART-Seq2 from 8 samples: (1-2) primary cultured oculomotor/trochlear motor neurons and spinal motor neurons collected at embryonic day E11.5 and cultured for 7 days, (3-8) ESC-derived induced cranial and spinal motor neurons at either 2 days, 5 days, or 7 days after plating.

Publication Title

Stem cell-derived cranial and spinal motor neurons reveal proteostatic differences between ALS resistant and sensitive motor neurons.

Sample Metadata Fields

Specimen part, Subject

View Samples
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refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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