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accession-icon GSE15516
Immunomodulatory function of bone marrow-derived mesenchymal stem cells in experimental autoimmune type 1 diabetes
  • organism-icon Mus musculus
  • sample-icon 8 Downloadable Samples
  • Technology Badge IconIllumina mouse-6 v1.1 expression beadchips

Description

Human clinical trials in type 1 diabetes (T1D) patients are underway using mesenchymal stem cells (MSC) without prior validation in a mouse model for the disease. In response to this void, we characterized bone marrow-derived murine MSC for their ability to modulate immune responses in the context of T1D, as represented in non-obese diabetic (NOD) mice. In comparison to NOD-, BALB/c-MSC express higher levels of the negative costimulatory molecule PD-L1 and promote a shift toward Th2-like responses in treated NOD mice. In addition, transfer of MSC from resistant strains (i.e. NOR or BALB/c), but not from NOD mice, conferred disease protection when administered to prediabetic NOD mice. The number of BALB/c-MSC trafficking to the pancreatic lymph nodes of NOD mice was higher than in NOD mice provided autologous NOD-MSC. Administration of BALB/c-MSC resulted in reversal of hyperglycemia in 90% of NOD mice (p=0.002). Transfer of autologous NOD-MSC imparted no such therapeutic benefit, and in fact soft tissue and visceral tumors were uniquely observed in this setting (i.e. no tumors were present with BALB/c- or NOR-MSC transfer). These data provide important preclinical data supporting the basis for further development of allogeneic MSC-based therapies for T1D and potentially, other autoimmune disorders.

Publication Title

Immunomodulatory function of bone marrow-derived mesenchymal stem cells in experimental autoimmune type 1 diabetes.

Alternate Accession IDs

E-GEOD-15516

Sample Metadata Fields

No sample metadata fields

View Samples
accession-icon GSE7658
Gene Expression Profile of Hematopoietic Stem Cells during Zebrafish Development
  • organism-icon Danio rerio
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Zebrafish Genome Array (zebrafish)

Description

In order to detect transcriptional differences between primitive and definitive hematopoietic stem and progenitor cells during regular development in the zebrafish embryo, gata1-GFP+/+(18 somites), lmo2-GFP+/+ (18 somites and 35 hpf)1 and cd41-GFP+/+ (35 hpf) cells from transgenic embryos were individually separated from GFP-/- cells by flow cytometry at the indicated stages. For each individual population, pools of 600 - 1500 transgenic embryos were collected. After RNA extraction, labelled cRNA was hybridized onto Affymetrix microarrays. Individual experiments were performed with 2 or 3 biological replicates.

Publication Title

No associated publication

Alternate Accession IDs

E-GEOD-7658

Sample Metadata Fields

Age

View Samples
accession-icon GSE31092
Expression analysis of ZBP-89 deficient human primary erythroid progenitors
  • organism-icon Homo sapiens
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133A 2.0 Array (hgu133a2)

Description

The molecular mechanisms underlying erythroid-specific gene regulation remain incompletely understood. Closely spaced binding sites for GATA, NF-E2/maf and CACCC interacting transcription factors play functionally important roles in globin and other erythroid-specific gene expression. We and others recently identified the CACCC-binding transcription factor ZBP-89 as a novel GATA-1 and NF-E2/mafK interacting partner. Here, we examined the role of ZBP-89 in human globin gene regulation and erythroid maturation using a primary CD34+ cell ex vivo differentiation system. We show that ZBP-89 protein levels rise dramatically during human erythroid differentiation, and that ZBP-89 occupies key cis-regulatory elements within the globin and other erythroid gene loci. ZBP-89 binding correlates strongly with RNA Pol II occupancy, active histone marks, and high-level gene expression. ZBP-89 physically associates with the histone acetyltransferases (HATs) p300 and Gcn5/Trrap, and occupies common sites with Gcn5 within the human globin loci. Lentiviral shRNA knockdown of ZBP-89 results in reduced Gcn5 occupancy, decreased acetylated histone 3 levels, lower globin and erythroid-specific gene expression, and impaired erythroid maturation. Addition of the HDAC inhibitor valproic acid partially reverses the reduced globin gene expression. These findings reveal an activating role for ZBP-89 in human globin gene regulation and erythroid differentiation.

Publication Title

Role of ZBP-89 in human globin gene regulation and erythroid differentiation.

Alternate Accession IDs

E-GEOD-31092

Sample Metadata Fields

Specimen part

View Samples
accession-icon GSE42250
Genome-wide analysis reveals TET- and TDG-mediated 5-methylcytosine oxidation dynamics
  • organism-icon Mus musculus
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

Ten-eleven translocation (Tet) family of DNA dioxygenases converts 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5- carboxylcytosine (5caC) through iterative oxidation reactions. While 5mC and 5hmC are relatively abundant, 5fC and 5caC are at very low levels in the mammalian genome. Thymine DNA glycosylase (TDG) and base excision repair (BER) pathways can actively remove 5fC/5caC to regenerate unmethylated cytosine, but it is unclear to what extent and at which part of the genome such active demethylation processes take place. Here, we have performed high-throughput sequencing analysis of 5mC/5hmC/5fC/5caC- enriched DNA using modification-specific antibodies and generated genome-wide distribution maps of these cytosine modifications in wild-type and Tdg-deficient mouse embryonic stem cells (ESCs). We observe that the steady state 5fC and 5caC are preferentially detected at repetitive sequences in wild-type mouse ESCs. Depletion of TDG causes marked accumulation of 5fC and 5caC at a large number of distal gene regulatory elements and transcriptionally repressed/poised gene promoters, suggesting that Tet/TDG-dependent dynamic cycling of 5mC oxidation states may be involved in regulating the function of these regions. Thus, comprehensive mapping of 5mC oxidation and BER pathway activity in the mammalian genome provides a promising approach for better understanding of biological roles of DNA methylation and demethylation dynamics in development and diseases.

Publication Title

Genome-wide analysis reveals TET- and TDG-dependent 5-methylcytosine oxidation dynamics.

Alternate Accession IDs

E-GEOD-42250

Sample Metadata Fields

Specimen part

View Samples
accession-icon GSE41316
Kdm2b maintains murine embryonic stem cell status by recruiting PRC1 complex to CpG islands of developmental genes
  • organism-icon Mus musculus
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Kdm2b maintains murine embryonic stem cell status by recruiting PRC1 complex to CpG islands of developmental genes.

Alternate Accession IDs

E-GEOD-41316

Sample Metadata Fields

Specimen part, Cell line

View Samples
accession-icon GSE46112
Genome-wide analysis reveals TET- and TDG-mediated 5-methylcytosine oxidation dynamics [Expression]
  • organism-icon Mus musculus
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

Ten-eleven translocation (Tet) family of DNA dioxygenases converts 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5- carboxylcytosine (5caC) through iterative oxidation reactions. While 5mC and 5hmC are relatively abundant, 5fC and 5caC are at very low levels in the mammalian genome. Thymine DNA glycosylase (TDG) and base excision repair (BER) pathways can actively remove 5fC/5caC to regenerate unmethylated cytosine, but it is unclear to what extent and at which part of the genome such active demethylation processes take place. Here, we have performed high-throughput sequencing analysis of 5mC/5hmC/5fC/5caC- enriched DNA using modification-specific antibodies and generated genome-wide distribution maps of these cytosine modifications in wild-type and Tdg-deficient mouse embryonic stem cells (ESCs). We observe that the steady state 5fC and 5caC are preferentially detected at repetitive sequences in wild-type mouse ESCs. Depletion of TDG causes marked accumulation of 5fC and 5caC at a large number of distal gene regulatory elements and transcriptionally repressed/poised gene promoters, suggesting that Tet/TDG-dependent dynamic cycling of 5mC oxidation states may be involved in regulating the function of these regions. Thus, comprehensive mapping of 5mC oxidation and BER pathway activity in the mammalian genome provides a promising approach for better understanding of biological roles of DNA methylation and demethylation dynamics in development and diseases.

Publication Title

Genome-wide analysis reveals TET- and TDG-dependent 5-methylcytosine oxidation dynamics.

Alternate Accession IDs

E-GEOD-46112

Sample Metadata Fields

Specimen part

View Samples
accession-icon GSE41298
Kdm2b maintains murine embryonic stem cell status by recruiting PRC1 complex to CpG islands of lineage genes [Expression profiling]
  • organism-icon Mus musculus
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

Polycomb group (PcG) proteins play important roles in repressing lineage-specific genes and maintaining the undifferentiated state of mouse embryonic stem cells (mESCs). However, the mechanisms by which PcG proteins are recruited to their targets are largely unknown. Here, we show that the histone demethylase Kdm2b is highly expressed in mESCs and regulated by the pluripotent factors Oct4/Sox2 directly. Depletion of Kdm2b in mESCs causes de-repression of lineage-specific genes and induces early differentiation. The function of Kdm2b depends on its CXXC-ZF domain, which mediates Kdm2bs genome-wide binding to CpG islands (CGIs). Kdm2b interacts with the core components of the Polycomb repressive complex 1 (PRC1) and recruits the complex to the CGIs of early lineage-specific genes. Thus, our study not only reveals a novel Oct4/Sox2-Kdm2b-PRC1-CGI regulatory axis and its function in maintaining undifferentiated state of mESCs, but also demonstrates a critical function of Kdm2b in recruiting PRC1 to the CGIs of lineage-specific genes to repress their expression.

Publication Title

Kdm2b maintains murine embryonic stem cell status by recruiting PRC1 complex to CpG islands of developmental genes.

Alternate Accession IDs

E-GEOD-41298

Sample Metadata Fields

Specimen part, Cell line

View Samples
accession-icon GSE11261
Study of activity-regulated genes in mouse primary cultured neurons
  • organism-icon Mus musculus
  • sample-icon 33 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Expression 430A Array (moe430a), Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Mouse Expression 430B Array (moe430b)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Activity-dependent regulation of inhibitory synapse development by Npas4.

Alternate Accession IDs

E-GEOD-11261

Sample Metadata Fields

No sample metadata fields

View Samples
accession-icon GSE11258
Npas4-regulated genes in mouse hippocampal neurons
  • organism-icon Mus musculus
  • sample-icon 23 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Mouse Expression 430A Array (moe430a)

Description

we performed a DNA microarray experiment to identify activity-regulated genes that are misregulated in the absence of Npas4.

Publication Title

Activity-dependent regulation of inhibitory synapse development by Npas4.

Alternate Accession IDs

E-GEOD-11258

Sample Metadata Fields

No sample metadata fields

View Samples
accession-icon GSE11256
KCl depolarization-regulated genes in mouse cortical neurons
  • organism-icon Mus musculus
  • sample-icon 10 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Expression 430A Array (moe430a), Affymetrix Mouse Expression 430B Array (moe430b)

Description

we used DNA microarray analysis to identify genes that are induced by neuronal activity in excitatory neurons at the time when inhibitory synapses are forming and maturing on them.

Publication Title

Activity-dependent regulation of inhibitory synapse development by Npas4.

Alternate Accession IDs

E-GEOD-11256

Sample Metadata Fields

No sample metadata fields

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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Developed by the Childhood Cancer Data Lab

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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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