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accession-icon SRP103009
mTORC1 balances cellular amino acid supply with demand for protein synthesis through post-transcriptional control of ATF4
  • organism-icon Homo sapiens
  • sample-icon 18 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000

Description

The mammalian target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth that is commonly deregulated in human diseases. Here we find that mTORC1 controls a transcriptional program encoding amino acid transporters and metabolic enzymes through a mechanism also used to regulate protein synthesis. Bioinformatic analysis of mTORC1-responsive mRNAs identified a promoter element recognized by activating transcription factor 4 (ATF4), a key effector of the integrated stress response. ATF4 translation is normally induced by phosphorylation of eukaryotic initiation factor 2 alpha (eIF2a) through a mechanism that requires upstream open reading frames (uORFs) in the ATF4 5'' UTR. mTORC1 also controls ATF4 translation through uORFs, but independent of changes in eIF2a phosphorylation. mTORC1 instead employs the 4E-binding protein (4E-BP) family of translation repressors. These results link mTORC1-regulated demand for protein synthesis with an ATF4-regulated transcriptional program that controls the supply of amino acids to the translation machinery. Overall design: RNA-seq analysis of wild-type and ATF4-null HEK293T cells treated with Torin 1 or tunicamycin for 6 h, and ribosome profiling analysis of HEK293T cells treated with Torin 1 for 24 h.

Publication Title

mTORC1 Balances Cellular Amino Acid Supply with Demand for Protein Synthesis through Post-transcriptional Control of ATF4.

Sample Metadata Fields

Subject

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accession-icon GSE79287
Correlative Controls of Seeds over Maternal Growth and Senescence in Arabidopsis (expression)
  • organism-icon Arabidopsis thaliana
  • sample-icon 14 Downloadable Samples
  • Technology Badge Icon Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)

Description

Correlative controls (influences of one organ over another organ) of seeds over maternal growth are one of the most obvious phenotypic expressions of the trade-off between growth and reproduction. However, the underlying molecular mechanisms are largely unknown. Here, we characterize the physiological and molecular effects of correlative inhibition by seeds on Arabidopsis thaliana inflorescences, i.e. global proliferative arrest (GPA) during which all maternal growth ceases upon the production of a given number of seeds. We use laser-assisted microdissection and RNA-seq or Affymetrix GeneChip hybridizations to compare sterile growing, fertile growing and fertile arrested meristems or whole inflorescences. In shoot tissues, we detected the induction of stress- and senescence-related gene expression upon fruit production and GPA, and a drop in chlorophyll levels - suggestive of altered source-sink relationships between vegetative shoot and reproductive tissues. Levels of shoot reactive oxygen species, however, strongly decreased upon GPA - a phenomenon that is associated with bud dormancy in some perennials. Indeed, gene expression changes in arrested apical inflorescences after fruit removal resembled changes observed in axillary buds following release from apical dominance. This suggests that GPA represents a form of bud dormancy, and that dominance is gradually transferred from growing inflorescences to maturing seeds - allowing offspring control over maternal resources, simultaneously restricting offspring number.

Publication Title

Seed Production Affects Maternal Growth and Senescence in Arabidopsis.

Sample Metadata Fields

No sample metadata fields

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accession-icon SRP018933
Small RNA profiling of human cumulus cells and oocytes
  • organism-icon Homo sapiens
  • sample-icon 2 Downloadable Samples
  • Technology Badge IconIllumina Genome Analyzer II

Description

Cumulus cells are biologically distinct from other follicular cells and perform specialized roles, transmitting signals within the ovary and supporting oocyte maturation during follicular development. The bi-directional communication between the oocyte and the surrounding cumulus cells is crucial for the acquisition of oocyte competence. Using Illumina/deep-sequencing technology, we dissected the small RNAome of pooled human mature MII oocytes and cumulus cells. Overall design: Cumulus cells and MII mature oocytes small RNA profiles were generated by deep-sequencing, using Illumina 1G sequencer

Publication Title

MicroRNAs: new candidates for the regulation of the human cumulus-oocyte complex.

Sample Metadata Fields

Specimen part, Subject

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accession-icon GSE52451
Translational regulation of specific mRNAs controls feedback inhibition and survival during macrophage activation
  • organism-icon Mus musculus
  • sample-icon 16 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000, Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Translational regulation of specific mRNAs controls feedback inhibition and survival during macrophage activation.

Sample Metadata Fields

Specimen part, Time

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accession-icon GSE52449
Translational regulation of specific mRNAs controls feedback inhibition and survival during macrophage activation [array]
  • organism-icon Mus musculus
  • sample-icon 16 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000, Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

When macrophages encounter pathogens, they transiently induce an orchestrated cascade of pro- and anti-inflammatory genes. We systematically analyzed the contribution of translational regulation to the early phase of macrophage activation. While the expression of most cytokines is regulated by changes in mRNA levels, de-repression of translation was found to permit expression of many feedback inhibitors of the inflammatory response. This includes NF-kB inhibitors (IkBd, IkBz, Nr4a1, Ier3), a p38 MAPK antagonist (Dusp1) and post-transcriptional suppressors of cytokine expression (TTP and Zc3h12a). Ier3 is tightly co-regulated with TNF at the level of mRNA abundance and translation. Macrophages lacking Ier3 show reduced survival upon activation, indicating that induction of Ier3 is required to protect macrophages from lipopolysaccharide-induced cell death. Our analysis reveals an important role of translational regulation in the resolution of inflammation and macrophage survival.

Publication Title

Translational regulation of specific mRNAs controls feedback inhibition and survival during macrophage activation.

Sample Metadata Fields

Specimen part

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accession-icon GSE24348
Expression data of Arabidopsis thaliana wild-type plants and quadruple nas T-DNA insertion mutants grown under different Fe supply conditions
  • organism-icon Arabidopsis thaliana
  • sample-icon 24 Downloadable Samples
  • Technology Badge Icon Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)

Description

Essential metals such as iron are required for healthy plant growth. Fe is an important cofactor and catalytic element in many biological processes. Fe and other metals can also be toxic when present in excess. Therefore plants have mechanisms of metal homeostasis which involve coordination of metal ion transporters for uptake, translocation and compartmentalisation. The NAS genes are supposed to play an important role in Fe homeostasis. They are coding for enzymes called nicotianaminesynthase (NAS), which synthesize nicotianamine (NA) by a one-step condensation reaction of three molecules S-adenosyl-methionine. NA acts as a chelator for Fe, Cu, Ni and Zn and might be involved in the transport and allocation of Fe throughout the plant. We generated quadruple T-DNA insertion mutant nas plants to investigate NA function as described in Klatte et al., 2009, Plant Physiol. The nas4x-1 plants show an interveinal leaf chlorosis when turning from vegetative to reproductive stage, which intensifies when growing under Fe deficiency conditions. nas4x-1 plants have strongly reduced NA contents and show an elevated Fe deficiency response in roots. By performing microarray experiments we want to reveal global changes on transcriptional level in roots and leaves of nas4x-1 mutant compared to wild type plants grown under Fe supply and Fe deficiency conditions, respectively. The loss of NAS genes has a strong impact on the regulation of other metal homeostasis genes and allows to draw conclusions about nicotianamine function in metal homeostasis of A.thaliana.

Publication Title

Transcriptome analysis by GeneTrail revealed regulation of functional categories in response to alterations of iron homeostasis in Arabidopsis thaliana.

Sample Metadata Fields

Specimen part

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accession-icon SRP032963
High temporal resolution of mRNA expression patterns during the early macrophage response to LPS [RNA_Seq]
  • organism-icon Mus musculus
  • sample-icon 8 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000

Description

When macrophages encounter pathogens, they transiently induce an orchestrated cascade of pro- and anti-inflammatory genes. To obtain a precise picture of transcriptome-wide mRNA expression patterns, we performed RNA-Seq of total RNA at a high temporal resolution during the first two hours of macrophage activation. We systematically analyzed the contribution of translational regulation to the early phase of macrophage activation. While the expression of most cytokines is pre-dominanatly regulated by changes in mRNA levels, de-repression of translation was found to permit expression of many feedback inhibitors of the inflammatory response. Overall design: Expression profiles of LPS-treated Raw264.7 cells (0, 15, 30, 45, 60, 75, 90 and 120 min after stimulation) were generated by deep sequencing using Illumina HiSeq 2000.

Publication Title

Translational regulation of specific mRNAs controls feedback inhibition and survival during macrophage activation.

Sample Metadata Fields

No sample metadata fields

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accession-icon SRP131761
Spatial and single-cell transcriptional profiling identifies functionally distinct human dermal fibroblast subpopulations
  • organism-icon Homo sapiens
  • sample-icon 189 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500, Illumina HiSeq 2000

Description

Fibroblasts synthesize the extracellular matrix of connective tissue and play an essential role in maintaining tissue integrity. We have previously shown that mouse skin connective tissue, the dermis, is comprised of functionally distinct fibroblast lineages. However, the extent of fibroblast heterogeneity in human skin is unknown. Here, using a combination of spatial transcriptional profiling of human and mouse dermis and single cell transcriptional profiling of human dermal fibroblasts, we show that there are at least four distinct fibroblast populations in adult human skin. We define markers permitting prospective isolation of these cells and show that although marker expression is rapidly lost in culture, different fibroblast subpopulations retain distinct functionality in terms of Wnt signalling, T cell communication and the ability to support human epidermal reconstitution in organotypic culture. Furthermore, while some fibroblast subpopulations are spatially segregated, others are not. These findings have profound implications for normal wound healing and diseases characterized by excessive fibrosis, and suggest that ex vivo expansion or in vivo ablation of specific fibroblast subpopulations may have therapeutic applications. Overall design: Spatial RNA sequencing of human papillary versus reticular dermis for 3 individuals, and single cell RNA sequencing of dermal fibroblasts for a single individual.

Publication Title

Spatial and Single-Cell Transcriptional Profiling Identifies Functionally Distinct Human Dermal Fibroblast Subpopulations.

Sample Metadata Fields

Specimen part, Subject

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accession-icon GSE104225
Spatial and single-cell transcriptional profiling identifies functionally distinct human dermal fibroblast subpopulations
  • organism-icon Mus musculus
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 2.0 ST Array (mogene20st)

Description

Expression data from P2 mouse fibroblasts sorted for CD26, Sca1 and Dlk1. We have sorted mouse fibroblasts using the different lineages markers

Publication Title

Spatial and Single-Cell Transcriptional Profiling Identifies Functionally Distinct Human Dermal Fibroblast Subpopulations.

Sample Metadata Fields

Specimen part

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accession-icon GSE48624
The effect of listening to music on human transcriptome
  • organism-icon Homo sapiens
  • sample-icon 96 Downloadable Samples
  • Technology Badge IconIllumina HumanHT-12 V4.0 expression beadchip

Description

The aim of the dataset was to study the effect of music exposure on human blood transcriptome.

Publication Title

The effect of listening to music on human transcriptome.

Sample Metadata Fields

Specimen part, Treatment, Race

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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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