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accession-icon GSE72875
Purification of functional human ES/iPSC-derived midbrain dopaminergic progenitors using LRTM1
  • organism-icon Mus musculus
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

Human induced pluripotent stem cells (iPSCs) can provide a promising source of midbrain dopaminergic (mDA) neurons for cell replacement therapy for Parkinson's disease (PD). However, iPSC-derived donor cells inevitably contain tumorigenic or inappropriate cells. To eliminate these unwanted cells, cell sorting using antibodies for specific markers such as CORIN or ALCAM have been developed, but neither marker is specific for ventral midbrain. Here, we employed a double-selection strategy for cells expressing both CORIN and LMX1A::GFP and report a novel cell surface marker to enrich mDA progenitors, LRTM1. When transplanted into 6-OHDA-lesioned rats, human iPSC-derived LRTM1+ cells survived and differentiated into mDA neurons in vivo, resulting in significant improvement in motor behavior without tumor formation. In addition, LRTM1+ cells exhibited efficient survival of mDA neurons in the brain of an MPTP-treated monkey. Thus, LRTM1 can provide a powerful tool for efficient and safe cell therapy for PD patients.

Publication Title

Purification of functional human ES and iPSC-derived midbrain dopaminergic progenitors using LRTM1.

Sample Metadata Fields

Specimen part

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accession-icon GSE145367
GeneChip Expression Array
  • organism-icon Rattus norvegicus
  • sample-icon 2 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Gene expression analysis to compare control cells and sorted cells

Publication Title

Identification of two major autoantigens negatively regulating endothelial activation in Takayasu arteritis.

Sample Metadata Fields

Specimen part

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accession-icon SRP102792
The histone H3 variant H3.3 regulates gene body DNA methylation in Arabidopsis thaliana [RNA-Seq]
  • organism-icon Arabidopsis thaliana
  • sample-icon 2 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000

Description

Gene bodies of vertebrates and flowering plants are occupied by histone variant H3.3 and DNA methylation. The origin and significance of these profiles remain largely unknown. The profiles of enrichments in DNA methylation and H3.3 over gene bodies are correlated and both depend similarly on gene transcription levels. This suggests a mechanistic link between H3.3 and gene body methylation. We engineered H3.3 knockdown in Arabidopsis and observed transcription reduction that predominantly affected genes responsive to environmental cues. When H3.3 levels were reduced, gene bodies showed a loss of DNA methylation correlated with transcription levels. To study the origin of changes in DNA methylation profiles when H3.3 levels are reduced, we examined genome wide distributions of several histone H3 marks, H2A.Z, linker histone H1 and nucleosome densities. We observed that in absence of H3.3, H1 distribution increased in gene bodies. This depends on levels of gene transcription. We propose that H3.3 prevents recruitment of H1, which in turn promotes chromatin folding and antagonizes access to DNA methyltransferases responsible for gene body methylation. Thus, gene body methylation is likely shaped by H3.3 dynamics in relation with transcriptional activity. Overall design: Examination of transcription in WT and H3.3 knock down samples by RNA-Seq

Publication Title

The histone H3 variant H3.3 regulates gene body DNA methylation in Arabidopsis thaliana.

Sample Metadata Fields

Subject

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accession-icon GSE41164
Expression data from splenic B-cells isolated from DmU50(HG-b) mice or wild-type C57BL/6J
  • organism-icon Mus musculus
  • sample-icon 2 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Box C/D-type small nucleolar RNAs (snoRNAs) are functional RNAs responsible for mediating 2-O-ribose methylation of ribosomal RNAs (rRNAs) within the nucleolus. Previously, in relation to a novel chromosomal translocation in a human B-cell lymphoma, we identified U50HG, a non-protein-coding gene that hosted a box C/D-type U50 snoRNA within its intron. To investigate the physiological importance of the U50 snoRNA and its involvement in tumorigenesis, we generated a mouse model deficient in mouse U50 (mU50) snoRNA expression without altering the expression of mouse mU50 host-gene, mU50HG-b. The established mU50 snoRNA-deficient mice showed a significant reduction of mU50 snoRNA expression and the corresponding target rRNA methylation in various organs. Lifelong phenotypic monitoring showed that the mU50-deficient mice looked almost normal without accelerated tumorigenicity; however, a notable difference was the propensity for anomalies in the lymphoid organs.

Publication Title

Generation of a mouse model with down-regulated U50 snoRNA (SNORD50) expression and its organ-specific phenotypic modulation.

Sample Metadata Fields

Specimen part

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accession-icon GSE12198
Primary NKcells vs. NKAES-derived NK cells vs. NKcells stimulated by low/high dose IL2 after 7days of culture
  • organism-icon Homo sapiens
  • sample-icon 16 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Transcriptional profiling of NKAES-derived NK cells after 7 days of culture compared to primary human NK cells and NK cells stimulated by low or high dose IL2 after 7 days of culture.

Publication Title

Expansion of highly cytotoxic human natural killer cells for cancer cell therapy.

Sample Metadata Fields

Specimen part

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accession-icon SRP181957
Molecular basis of neuronal subtype bias introduced by proneural factors Ascl1 and Neurog2 (single-cell RNA-seq)
  • organism-icon Mus musculus
  • sample-icon 4 Downloadable Samples
  • Technology Badge IconNextSeq 500

Description

Basic helix-loop-helix (bHLH) proneural transcription factors (TFs) Ascl1 and Neurog2 are integral to the development of the nervous system. Here, we investigated the molecular mechanisms by which Ascl1 and Neurog2 control the acquisition of generic neuronal fate and impose neuronal subtype identity. Using direct neuronal programming of embryonic stem cells, we found that Ascl1 and Neurog2 regulate distinct targets by binding to largely different sets of sites. Their divergent binding pattern is not determined by the previous chromatin state but distinguished by specific E-box enrichments which reflect the DNA sequence preference of the bHLH domain. The divergent Ascl1 and Neurog2 binding patterns result in distinct chromatin accessibility and enhancer activity landscapes that shape the binding and activity of downstream TFs during neuronal specification. Our findings suggest that proneural factors contribute to neuronal diversity by differentially altering the chromatin landscapes that shape the binding of neuronally expressed TFs. Overall design: Single-cell RNA-seq was used to characterize gene expression in mixed populations of mES cells containing induced expression of either Ascl1 or Neurog2.

Publication Title

Proneural factors Ascl1 and Neurog2 contribute to neuronal subtype identities by establishing distinct chromatin landscapes.

Sample Metadata Fields

Specimen part, Treatment, Subject

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accession-icon GSE43378
Expression data from glioma patients
  • organism-icon Homo sapiens
  • sample-icon 43 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

We used microarrays to select the genes associated glioma patients survival.

Publication Title

Gene expression signature-based prognostic risk score in patients with glioblastoma.

Sample Metadata Fields

Sex, Age, Disease, Disease stage

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accession-icon SRP074757
A multi-step transcriptional and chromatin cascade underlies motor neuron programming (single-cell RNA-seq)
  • organism-icon Mus musculus
  • sample-icon 768 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

Direct programming via the overexpression of transcription factors (TFs) aims to control cell fate at a precision that will be instrumental for clinical applications. However, direct programming of terminal fates remains an obscure process. Taking advantage of the rapid and uniquely efficient programming of spinal motor neurons by overexpression of Ngn2, Isl1 and Lhx3, we have characterized gene expression, chromatin and transcription factor binding time-course dynamics during complete motor neuron programming. Our studies point to a surprisingly dynamic programming process. Promoter chromatin and expression analysis reveals at least three distinct phases of gene activation, while programming factor binding shifts from one set of targets to another, controlling regulatory region activity and gene expression. Furthermore, our evidence suggest that the enhancers and genes activated in the final stage of motor neuron processing are dependent on the combined activities of Isl1 and Lhx3 factors with Ebf and Onecut TFs that are themselves activated midway through the programming process. Our results suggest an unexpected multi-stage model of motor neuron programming in which the programming TFs require activation of a set of intermediate regulators before they complete the programming process. Overall design: Gene expression was characterized by single-cell RNA-seq during the direct programming of ES cells into motor neurons using over-expression of Ngn2-Isl1-Lhx3 programming factors.

Publication Title

A Multi-step Transcriptional and Chromatin State Cascade Underlies Motor Neuron Programming from Embryonic Stem Cells.

Sample Metadata Fields

Specimen part, Cell line, Treatment, Subject

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accession-icon SRP073703
A multi-step transcriptional and chromatin cascade underlies motor neuron programming (RNA-Seq)
  • organism-icon Mus musculus
  • sample-icon 10 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

Direct programming via the overexpression of transcription factors (TFs) aims to control cell fate at a precision that will be instrumental for clinical applications. However, direct programming of terminal fates remains an obscure process. Taking advantage of the rapid and uniquely efficient programming of spinal motor neurons by overexpression of Ngn2, Isl1 and Lhx3, we have characterized gene expression, chromatin and transcription factor binding time-course dynamics during complete motor neuron programming. Our studies point to a surprisingly dynamic programming process. Promoter chromatin and expression analysis reveals at least three distinct phases of gene activation, while programming factor binding shifts from one set of targets to another, controlling regulatory region activity and gene expression. Furthermore, our evidence suggest that the enhancers and genes activated in the final stage of motor neuron processing are dependent on the combined activities of Isl1 and Lhx3 factors with Ebf and Onecut TFs that are themselves activated midway through the programming process. Our results suggest an unexpected multi-stage model of motor neuron programming in which the programming TFs require activation of a set of intermediate regulators before they complete the programming process. Overall design: For bulk cell RNA-seq analysis, cells were collected at different time points after NIL induction and RNA isolated using TRIzol LS (Life Technologies) followed by purification using Qiagen RNAeasy kit

Publication Title

A Multi-step Transcriptional and Chromatin State Cascade Underlies Motor Neuron Programming from Embryonic Stem Cells.

Sample Metadata Fields

Specimen part, Cell line, Subject

View Samples
accession-icon GSE34771
Expression data from primary central nervous system lymphoma (PCNSL) patients
  • organism-icon Homo sapiens
  • sample-icon 28 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

This study aimed to define the genes associated with PCNSL patient survival. Expression profiling was performed on 34 PCNSLs. A gene classifier was developed.

Publication Title

Gene expression signature-based prognostic risk score in patients with primary central nervous system lymphoma.

Sample Metadata Fields

Sex, Age, Specimen part, Disease, Disease stage

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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