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accession-icon SRP081516
Temperature regulates splicing efficiency of the cold-inducible RNA-binding protein gene Cirbp
  • organism-icon Mus musculus
  • sample-icon 22 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

In mammals body temperature fluctuates diurnally around a mean value of 36-37°C. Despite the small differences between minimal and maximal values, body temperature rhythms can drive robust cycles in gene expression in cultured cells and, likely, in, animals. Here we studied the mechanisms responsible for the temperature-dependent expression of Cold- Inducible RNA-Binding Protein (CIRBP). In NIH3T3 fibroblasts exposed to simulated mouse body temperature cycles Cirbp mRNA oscillates about 3-fold in abundance, as it does in mouse liver. This daily mRNA accumulation cycle is directly controlled by temperature oscillations and does not depend on the cells’ circadian clocks. Here, we show that the temperature-dependent accumulation of Cirbp mRNA is controlled primarily by the regulation of splicing efficiency, defined as the fraction of Cirbp pre-mRNA processed into mature mRNA. As revealed by genome-wide “approach-to-steady-kinetics”, this posttranscriptional mechanism is wide-spread in the temperature-dependent control of gene expression. Overall design: Cultured NIH3T3 cells seeded and kept at 37C degree for 4 hours before being switched to 33C and 38C. After 16 hours of incubation the temperature was shifted to 38C and 33C, respectively. Sample were then taken at 0, 1, 3, 6 and 9 hour after the temperature shift. Paired-end, strand-specific, total RNA-seq was performed over the samples at the respective time points using the Illumina HiSeq2500 platform.

Publication Title

Temperature regulates splicing efficiency of the cold-inducible RNA-binding protein gene Cirbp.

Sample Metadata Fields

Specimen part, Subject, Time

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accession-icon GSE80522
The genomic context and co-recruitment of SP1 affect ERR co-activation by PGC-1 in muscle cells
  • organism-icon Mus musculus
  • sample-icon 9 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

The Genomic Context and Corecruitment of SP1 Affect ERRα Coactivation by PGC-1α in Muscle Cells.

Sample Metadata Fields

Specimen part

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accession-icon GSE98490
Identification of GRF9 early responding genes using an estradiol-inducible overexpression (XVE) system.
  • organism-icon Arabidopsis thaliana
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)

Description

The aim of the experiment was to identify genes rapidly responding at their expression level to enhanced expression of the transcription factor GRF9.

Publication Title

GROWTH-REGULATING FACTOR 9 negatively regulates arabidopsis leaf growth by controlling ORG3 and restricting cell proliferation in leaf primordia.

Sample Metadata Fields

Age, Specimen part

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accession-icon SRP189995
scRNA-seq analysis of the dual expressors, B cells and T cells of a diabetes patient
  • organism-icon Homo sapiens
  • sample-icon 77 Downloadable Samples
  • Technology Badge IconNextSeq 500

Description

We identified a rare subset of autoreactive lymphocytes with a hybrid phenotype of T and B cells including coexpression of TCR and BCR and key lineage markers of both cell types (hereafter referred to as dual expressers or DEs). To investigate the dual phenotype of DEs at single cell resolution, we examined their transcriptomes using single cell RNA sequencing (scRNA-seq). We sorted individual DEs, Bcon and Tcon cells from PBMCs of one type I diabetes patient and analyzed the transcriptomes of 34 DEs, 20 Bcon , and 23 Tcon using the plate-based SMART-seq2 protocol (Tirosh and Suva, 2018; Tirosh et al., 2016). Our results show that DEs have uniquely expressed genes along with genes encoding lineage markers of T and B cells. Overall design: Examination of the transcriptomes of three cell types, Des (Dual Expressors), Bcon (Conventional B) and Tcon (Conventional T) cells from the PBMCs of one type I diabetes patient

Publication Title

A Public BCR Present in a Unique Dual-Receptor-Expressing Lymphocyte from Type 1 Diabetes Patients Encodes a Potent T Cell Autoantigen.

Sample Metadata Fields

Specimen part, Disease, Subject

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accession-icon GSE49274
Antigen availability determines CD8+ T cell-dendritic cell interaction kinetics and T cell fate decisions.
  • organism-icon Mus musculus
  • sample-icon 35 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

This experiment compares the transciptional changes in antigen specific murine CD8 T cells (P14 T cells) after exposure in vivo to dendritic cells (DC) pulsed with low dose cognate peptide (1uM KAVYNFATC), high dose cognate peptide (100uM KAVYNFATC) or no antigen. Splenic dendritic cells were freshly isolated, peptide pulsed, washed and then adoptively transferred s.c. to the right footpad of C57BL/6 hosts. After 18h, freshly isolated P14 CD8 T cells were labelled with CMFDA and adoptively transferred iv. Two hours after T cell transfer, anti-L selectin antibody was given iv. At 12 and 24 hours, recipients were sacrificed and The right popliteal LN was harvested at 12 or 24h post T cell transfer and a single cell suspension was created and stained with PE CD4, B220 and CD19 (dump channel). Cells were then sorted on a FacsARIA for being non-doublets, CMFDA positive and dump channel negative.

Publication Title

Antigen availability determines CD8⁺ T cell-dendritic cell interaction kinetics and memory fate decisions.

Sample Metadata Fields

No sample metadata fields

View Samples
accession-icon GSE74854
Id2 is required for antiviral Th1 cell differentiation and represses Tfh cell differentiation
  • organism-icon Mus musculus
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

Differentiation of naive CD4+ T cells into T-helper (Th) effector subsets is critical for protection against pathogens. Together, E-protein transcription factors and the inhibitor-of-DNA binding (Id) proteins are important arbiters of T cell development, but their role in the differentiation of Th1 and Tfh cells is not well understood. Th1 cells show robust Id2 expression compared to Tfh cells, and RNAi depletion of Id2 increased Tfh cell frequencies and germinal center responses, while impairing Th1 cell accumulation during viral infection. Further, Th1 cell differentiation was blocked by genetic ablation of Id2, leading to E-protein dependent accumulation of effector cells with 78% of Th1-associated genes showing diminished expression and a concurrent enrichment of the Tfh gene-expression program. The Tfh-defining transcriptional repressor Bcl6 bound to the Id2 locus inhibiting expression, providing a mechanism by which bimodal expression of Id2 in Tfh and Th1 cells can be established. Thus, Id2 is critical in enforcing the reciprocal development of Th1 and Tfh cell fates.

Publication Title

Id2 reinforces TH1 differentiation and inhibits E2A to repress TFH differentiation.

Sample Metadata Fields

Age, Specimen part

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accession-icon GSE71306
Scl-Ab: Exploratory 26-Week Subcutaneous Toxicology Study in the Aged Ovariectomized Female Sprague Dawley Rat with an 18-week Recovery [vertebrae]
  • organism-icon Rattus norvegicus
  • sample-icon 294 Downloadable Samples
  • Technology Badge Icon Affymetrix Rat Genome 230 2.0 Array (rat2302)

Description

This study is designed to compare and contrast the temporal and spatial changes in bone formation rates and transcriptional profiles in cortical and cancellous bone cell populations enriched by laser capture microdissection (LCM) in ovariectomized rats administered Scl-Ab by subcutaneous injection for up to 26 consecutive weeks, followed by a recovery period of up to 18 weeks.

Publication Title

Time-dependent cellular and transcriptional changes in the osteoblast lineage associated with sclerostin antibody treatment in ovariectomized rats.

Sample Metadata Fields

Sex, Specimen part, Time

View Samples
accession-icon GSE107395
Runx3 programs CD8+ T cell residency in non-lymphoid tissues and tumours
  • organism-icon Mus musculus
  • sample-icon 20 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

Runx3 programs CD8<sup>+</sup> T cell residency in non-lymphoid tissues and tumours.

Sample Metadata Fields

Specimen part, Time

View Samples
accession-icon GSE107278
Microarray analysis of CD8+ T cell subsets during LCMV infection
  • organism-icon Mus musculus
  • sample-icon 20 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

Tissue-resident memory CD8+T cells (Trm) are positioned at common sites of pathogen exposure where they elicit rapid and robust protective immune responses1,2. However, the molecular signals controlling Trm differentiation and homeostasis are not fully understood. Here we show that mouse Trm precursor cells represent a unique CD8+T cell subset that is distinct from the precursors of circulating memory populations at the levels of gene expression and chromatin accessibility. Exploiting computational and functional RNAiin vivoscreens, we identified the transcription factor (TF) Runx3 as a key regulator of Trm differentiation and homeostasis. Runx3 was required to establish Trm populations in diverse tissue environments and supported expression of critical tissue-residency genes while suppressing genes associated with tissue egress and recirculation. Analysis of the accessibility of Runx3 target genes in Trm-precursor cells revealed a distinct regulatory role for Runx3 in controlling Trm differentiation despite relatively widespread and uniform expression among all CD8+T cell subsets.Further, we show that human and murine tumor-infiltrating lymphocytes (TIL) share a core tissue-residency gene-expression signature with Trm. In a mouse model of adoptive T cell therapy for melanoma, Runx3-deficient CD8+TIL failed to accumulate in tumors, resulting in greater rates of tumor growth and mortality. Conversely, overexpression of Runx3 enhanced TIL abundance, delayed tumor growth, and prolonged survival. In addition to establishing Runx3 as a central regulator of Trm differentiation, these results provide novel insight into the signals that promote T cell residency in tissues, which could be leveraged to enhance vaccine efficacy or adoptive cell therapy treatments that target cancer.

Publication Title

Runx3 programs CD8<sup>+</sup> T cell residency in non-lymphoid tissues and tumours.

Sample Metadata Fields

Specimen part, Time

View Samples
accession-icon SRP125508
RNA-Seq of CD8+ T cell subsets during LCMV infection
  • organism-icon Mus musculus
  • sample-icon 8 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

Tissue-resident memory CD8+ T cells (Trm) are positioned at common sites of pathogen exposure where they elicit rapid and robust protective immune responses1,2. However, the molecular signals controlling Trm differentiation and homeostasis are not fully understood. Here we show that mouse Trm precursor cells represent a unique CD8+ T cell subset that is distinct from the precursors of circulating memory populations at the levels of gene expression and chromatin accessibility. Exploiting computational and functional RNAi in vivo screens, we identified the transcription factor (TF) Runx3 as a key regulator of Trm differentiation and homeostasis. Runx3 was required to establish Trm populations in diverse tissue environments and supported expression of critical tissue-residency genes while suppressing genes associated with tissue egress and recirculation. Analysis of the accessibility of Runx3 target genes in Trm-precursor cells revealed a distinct regulatory role for Runx3 in controlling Trm differentiation despite relatively widespread and uniform expression among all CD8+ T cell subsets. Further, we show that human and murine tumor-infiltrating lymphocytes (TIL) share a core tissue-residency gene-expression signature with Trm. In a mouse model of adoptive T cell therapy for melanoma, Runx3-deficient CD8+ TIL failed to accumulate in tumors, resulting in greater rates of tumor growth and mortality. Conversely, overexpression of Runx3 enhanced TIL abundance, delayed tumor growth, and prolonged survival. In addition to establishing Runx3 as a central regulator of Trm differentiation, these results provide novel insight into the signals that promote T cell residency in tissues, which could be leveraged to enhance vaccine efficacy or adoptive cell therapy treatments that target cancer. Overall design: 8 samples, 2 replicates each, naïve P14 cells or Day 7 LCMV infection CD8+ T cell subsets

Publication Title

Runx3 programs CD8<sup>+</sup> T cell residency in non-lymphoid tissues and tumours.

Sample Metadata Fields

Specimen part, Cell line, Subject

View Samples

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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