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accession-icon GSE28186
Expression data from from the E9.25 hearts of mouse embryos
  • organism-icon Mus musculus
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Congenital heart defects (CHDs) occur in 0.51% of live births, yet the underlying genetic etiology remains mostly unknown. Recently, a new source of myocardial cells, namely the second heart field (SHF), was discovered in the splanchnic mesoderm. Abnormal development of the SHF leads to a spectrum of outflow tract defects, such as persistent truncus arteriosus and tetralogy of Fallot. Intracellular Ca2+ signaling is known to be essential formany aspects of heart biology including heart development, but its role in the SHF is uncertain. Here, we analyzed mice deficient for genes encoding inositol 1,4,5-trisphosphate receptors (IP3Rs), which are intracellular Ca2+ release channels on the endo/sarcoplasmic reticulum that mediate Ca2+ mobilization. Mouse embryos that are double mutant for IP3R type 1 and type 3 (IP3R1/IP3R3/) show hypoplasia of the outflow tract and the right ventricle, reduced expression of specific molecular markers and enhanced apoptosis ofmesodermal cells in the SHF. Gene expression analyses suggest that IP3R-mediated Ca2+ signalingmay involve, at least in part, theMef2CSmyd1 pathway, a transcriptional cascade essential for the SHF. These data reveal that IP3R type 1 and type 3 may play a redundant role in the development of the SHF.

Publication Title

Inositol 1,4,5-trisphosphate receptors are essential for the development of the second heart field.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE18313
Expression data from cytotoxic T cell clone
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

T cells contribute to host-tumor interactions in patients with monoclonal gammopathies. Expansions of CD8+CD57+TCRV+ restricted cytotoxic T cell (CTL) clones are found in 48% of patients with multiple myeloma and confer a favorable prognosis. We now report the presence of CTL clones with varying TCRV repertoire in 70% of patients with Waldenstroms Macroglobulinaemia (WM) (n=20). Previous nucleoside analogue (NA) therapy, associated with an increased incidence of transformation to aggressive lymphoma, significantly influenced the presence of TCRV expansions (X2=11.6; P<0.001) as 83% of patients without (n=6) and only 7% with TCRV expansions (n=14) had received NA. Clonality of CD3+CD8+CD57+TCRV+ restricted CTLs were confirmed by TCRV CDR3 size analysis and direct sequencing. To characterize CTL clones, samples of CD3+CD8+CD57+TCRV+ cells were profiled using DNA microarrays and the results were validated on both gene and protein level. By gene set enrichment analysis, CTL clones not only expressed genes (GZMB, PRF1, FGFBP2) from cytotoxic pathways but also genes which suppress apoptosis, inhibit proliferation, arrest cell cycle G1/S transition and activate T cells (RAS, CSK and TOB pathways). Proliferation tracking confirmed their anergic state. Our studies demonstrate the incidence, NA sensitivity and anergic nature of clonal T cells in a B cell tumor.

Publication Title

Clonal expansions of cytotoxic T cells exist in the blood of patients with Waldenstrom macroglobulinemia but exhibit anergic properties and are eliminated by nucleoside analogue therapy.

Sample Metadata Fields

Specimen part

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accession-icon GSE34000
Expression data from the dorsal root ganglia during streptozotocin-induced painful diabetic neuropathy in rats
  • organism-icon Rattus norvegicus
  • sample-icon 9 Downloadable Samples
  • Technology Badge Icon Affymetrix Rat Expression 230A Array (rae230a)

Description

FK1706 potentiated nerve growth factor-induced neurite outgrowth, putatively mediated via FKBP-52 and the Ras/Raf/MAPK signaling pathway. It also improved mechanical allodynia accompanied by the recovery of intraepidermal nerve fiber density in a painful diabetic neuropathy in rats.

Publication Title

FK1706, a novel non-immunosuppressive immunophilin ligand, modifies gene expression in the dorsal root ganglia during painful diabetic neuropathy.

Sample Metadata Fields

Specimen part, Treatment

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accession-icon GSE65468
Analysis of Klf4 factor stoichiometry effects during iPS cell derivation from mouse embryonic fibroblasts
  • organism-icon Mus musculus
  • sample-icon 10 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

Oct3/4, Sox2, Klf4, and c-Myc re-wire somatic cells to achieve induced pluripotency (iPS cells). However, subtle differences in reprogramming methodology may confound comparative studies of reprogramming-induced gene expression changes. We specifically focused on the design of polycistronic reprogramming constructs, which encode all four factors linked with 2A peptides. Notably, publically available cassettes were found to employ one of two Klf4 variants (Klf4S and Klf4L; GenBank Accession Nos: AAC52939.1 and AAC04892.1), differing only by nine N-terminal amino acids. In a polycistronic context, these two variants generated dissimilar protein stoichiometry, where Klf4L vectors produced more Klf4 protein than those encoding Klf4S.

Publication Title

KLF4 N-terminal variance modulates induced reprogramming to pluripotency.

Sample Metadata Fields

Sex, Specimen part

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accession-icon GSE41688
Different levels of canonical Wnt signaling exert distinct roles in the colonic epithelium
  • organism-icon Mus musculus
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

There is a gradient of -catenin expression along the colonic crypt axis with the highest levels at the crypt bottom. However, it remains unclear whether different levels of canonical Wnt signaling exert distinct roles in the colonic epithelium. In the present study, we first showed that the canonical Wnt signaling is active in the proliferative compartment of normal colonic crypts by separating actively proliferating progenitor cells from non-proliferating cells in the colon using transgenic mice expressing a histone H2B-green fluorescent protein (GFP) fusion protein under the control of a tetracycline responsive regulatory element. Subsequently, we investigated the dose-dependent effect of canonical Wnt activation on colonic epithelial differentiation by controlling the expression levels of stabilized -catenin using a doxycycline-inducible transgenic system in mice. We show that elevated levels of Wnt signaling induce the amplification of Lgr5+ cells, which is accompanied by crypt fission and a reduction in cell proliferation among progenitor cells. In contrast, lower levels of -catenin induction enhanced cell proliferation rates of epithelial progenitors without affecting crypt fission rates. Notably, slow-cycling cells produced by -catenin activation exhibit activation of Notch signaling and the treatment of -catenin expressing mice with a Notch inhibitor turned such slow-cycling cells into actively proliferating cells. Our results indicate that the activation of the canonical Wnt signaling pathway is sufficient for de novo crypt formation, and suggest that different levels of canonical Wnt activations, in cooperation with Notch signaling, establish a hierarchy of slower-cycling stem cells and faster-cycling progenitor cells characteristic for the colonic epithelium.

Publication Title

Dose-dependent roles for canonical Wnt signalling in de novo crypt formation and cell cycle properties of the colonic epithelium.

Sample Metadata Fields

Sex, Specimen part

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accession-icon GSE17183
Hepatic gene expression before and during interferon and ribavirin combination therapy
  • organism-icon Homo sapiens
  • sample-icon 108 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Patients who cleared HCV viremia early during therapy tended to show favorable outcomes, whereas patients who needed a longer period to clear HCV had poorer outcomes. We explored the mechanisms of treatment resistance by comparing hepatic gene expression before and during treatment

Publication Title

Differential interferon signaling in liver lobule and portal area cells under treatment for chronic hepatitis C.

Sample Metadata Fields

Specimen part, Time

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accession-icon GSE89079
Gene expression analysis of mouse embryonic fibroblasts reprogrammed with OSK, Esrrb and Zic3
  • organism-icon Mus musculus
  • sample-icon 18 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

We report that Zic family (Zic1/2/3) and orphan nuclear receptors family (Esrrb and Nr5a2) transcription factors (TFs) synergistically enhance the reprogramming efficiency when transduced with Oct4, Sox2 and Klf4 (OSK) into murine fibroblasts. To identify the molecular mechanisms underlying this synergy, we analyzed global gene expression at 6 days after introduction of reprogramming factors. As a result, we found that primary targets of these TFs are different when either of TFs was introduced with OSK, but a significant portion of genes including pluripotency makers such as Dppa2 was synergistically upregulated. Further analysis revealed that metabolic pathways are the important targets of these TFs for efficient reprogramming.

Publication Title

Hybrid Cellular Metabolism Coordinated by Zic3 and Esrrb Synergistically Enhances Induction of Naive Pluripotency.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE28063
LEAFY target genes reveal a link between flower development and biotic stimulus response
  • organism-icon Arabidopsis thaliana
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

LEAFY target genes reveal floral regulatory logic, cis motifs, and a link to biotic stimulus response.

Sample Metadata Fields

Specimen part

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accession-icon GSE28062
LEAFY target genes reveal a link between flower development and biotic stimulus response (III)
  • organism-icon Arabidopsis thaliana
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)

Description

The transition from vegetative growth to flower formation is critical for the survival of flowering plants. The plant-specific transcription factor LEAFY (LFY) has central, evolutionarily conserved roles in this process, both in the formation of the first flower and later in floral patterning. We performed genome-wide binding and expression studies to elucidate the molecular mechanisms by which LFY executes these roles. Our study reveals that LFY directs an intricate regulatory network in control of floral homeotic gene expression and, unexpectedly, controls the expression of genes regulating the response to external stimuli in Arabidopsis. We further show that LFY dampens responses to a bacterial MAMP (microbe-associated molecular pattern) and to pathogen challenge. Our findings suggest a molecular mechanism for the coordination of reproductive stage development and disease response programs in plants. Regulation of these distinct survival programs by a single transcription factor may ensure optimal allocation of plant resources for reproductive fitness.

Publication Title

LEAFY target genes reveal floral regulatory logic, cis motifs, and a link to biotic stimulus response.

Sample Metadata Fields

Specimen part

View Samples
accession-icon GSE36814
Role for DNA methylation in response to Gata4 activation in embryonic stem cell-derived mesoderm
  • organism-icon Mus musculus
  • sample-icon 20 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

During embryogenesis, many key transcription factors are used repeatedly, achieving different outcomes depending on cell type and developmental stage. The epigenetic modification of the genome functions as a memory of a cells developmental history, and it has been proposed that such modification shapes the cellular response to transcription factors. To investigate the role of DNA methylation in the response to transcription factor Gata4, we examined expression profiles of Dnmt3a-/-Dnmt3b-/- ES cell-derived mesoderm cells cultured for 4 days with or without Gata4 activation, as well as the wild-type counterparts, using Affymetrix microarrays.

Publication Title

DNA methylation restricts lineage-specific functions of transcription factor Gata4 during embryonic stem cell differentiation.

Sample Metadata Fields

Specimen part

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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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