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accession-icon SRP095238
Transcriptome and Functional Analyses Reveal Roles For Regulators of Epigenetic States, Micro RNA Processing, And Long Non-Coding RNA In Myocyte Dedifferentiation: Insights Into Reprogramming A “Post-Mitotic” Cell
  • organism-icon Danio rerio
  • sample-icon 14 Downloadable Samples
  • Technology Badge IconIlluminaHiSeq2000

Description

Purpose: The ability of adult zebrafish tissues to undergo dedifferentiation provides an opportunity to probe the molecular underpinnings of cell identity and reprogramming. Zebafish muscle regeneration utilizes dedifferentiation to reprogram mature multinucleated myocytes into dedifferentiated myoblast that re-enter the cell cycle. A unique advantage of this system is that the regenerating cell mass is large and fairly homogenous, facilitating genomics approaches to uncovering the underlying biology. Methods: To better understand cellular reprogramming of mature myocytes, we temporally analyzed the changing transcriptome leading up to the proliferative switch. RNA was obtained after Laser Micro-dissection (LMD) of Control, 9 hour post-injury (HPI) or 18 HPI using Trizol and micro column purification. Illumina''s TruSeq Stranded mRNA Library Prep Kit and 0.1 - 4 µg total mRNA from pooled purified RNA samples were used for performing ribosomal-depletion (Ribo-Zero Gold rRNA Removal Kit, Illumina) and library preparation. Sequencing was performed by the UM DNA Sequencing Core, using an Illumina Hi-Seq 2000 (50-cycle, single end read) platform. Results: Clustering and functional annotation of differentially expressed genes highlighted the importance of catabolic and phagocytic processes upregulation at 9 and 18 hours post injury (hpi). Furthermore, genes encoding principle regulators of chromatin states were actively re-regulated during the reprogramming process. Utilizing the accessibility of these tissues in the zebrafish model, kKnockdown experiments enabled in vivo validation and phenotypic analysis of candidate genes and pathways for their roles in genomic and cellular reprogramming. Additionally, we found that despite of their low expression levels, lncRNAs were highly represented in gene clusters with dynamic, “switch-like” expression profiles, and that miRNA processing was also found important for reprogramming Conclusions: We conclude that reprogramming of a “post-mitotic” myocyte into a dedifferentiated myoblast requires both heritable yet nuanced epigenetic alterations and molecular switches that involve transcription factors, miRNA and lncRNA, while maintaining the lineage restriction of the cell of origin. Overall design: Early time points post injury (9 & 18 hours) mRNA and lncRNA profiles of Zebrafish lateral eye muscle (EOM) were generated by deep sequencing, in quadruplicate, using Illumina Hi-seq.

Publication Title

Temporally distinct transcriptional regulation of myocyte dedifferentiation and Myofiber growth during muscle regeneration.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE36664
Temporal transcriptional profiling of growth resumption following polyamine-depletion
  • organism-icon Mus musculus
  • sample-icon 24 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

Polyamines are absolutely required for cell growth and proliferation. While polyamine depletion results in reversible cell cycle arrest, the actual mechanism of growth inhibition is still obscure.

Publication Title

Expression profiling and biochemical analysis suggest stress response as a potential mechanism inhibiting proliferation of polyamine-depleted cells.

Sample Metadata Fields

Specimen part, Cell line

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accession-icon GSE36445
Temporal transcriptional profiling of polyamine-depleted NIH3T3 cells
  • organism-icon Mus musculus
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

Polyamines are absolutely required for cell growth and proliferation. While polyamine depletion results in reversible cell cycle arrest, the actual mechanism of growth inhibition is still obscure.

Publication Title

Expression profiling and biochemical analysis suggest stress response as a potential mechanism inhibiting proliferation of polyamine-depleted cells.

Sample Metadata Fields

Cell line, Time

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accession-icon GSE73705
OX40L protects against inflammation-driven fibrosis
  • organism-icon Mus musculus
  • sample-icon 7 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 2.0 ST Array (mogene20st)

Description

Fibrosis is a leading cause of deaths in industrialized countries and has no effective therapy. We demonstrated that blockade of OX40L prevented inflammation-driven fibrosis affecting the skin and the lungs and promotes regression of established dermal fibrosis in different murine models.

Publication Title

OX40L blockade protects against inflammation-driven fibrosis.

Sample Metadata Fields

Sex, Age, Specimen part, Treatment

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accession-icon GSE48536
Maize gene expression after infection of Ustilago maydis SG200 and SG200tin2
  • organism-icon Zea mays
  • sample-icon 9 Downloadable Samples
  • Technology Badge Icon Affymetrix Maize Genome Array (maize)

Description

Anthocyanin induction in plant is considered a general defense response against biotic and abiotic stresses. The infection by Ustilago maydis, the corn smut pathogen, is accompanied with anthocyanin induction in leaf tissue. We revealed that anthocyanin is intentionally induced by the virulence promoting secreted effector protein Tin2. Tin2 protein functions inside plant cells where it interacts with cytoplasmic maize protein kinase ZmTTK1. Tin2 masks an ubiquitin-proteasome degradation motif in ZmTTK1 leading to a more stable active kinase. Active ZmTTK1 controls transcriptional activation of genes in the anthocyanin biosynthesis pathway rerouting phenylalanine away from lignin biosynthesis.

Publication Title

A secreted Ustilago maydis effector promotes virulence by targeting anthocyanin biosynthesis in maize.

Sample Metadata Fields

Specimen part

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accession-icon SRP017811
Transcriptional Profiling of Mouse Uterus at Pre-implantation Stage under VEGF Repression
  • organism-icon Mus musculus
  • sample-icon 2 Downloadable Samples
  • Technology Badge IconIllumina Genome Analyzer

Description

In this study, a genetically repressed VEGF mouse model was used to analyze uterus transcriptome at G2.5 (gestation day 2.5) by Solexa/ Illumina’s digital gene expression (DGE) system. 831 uterus-specific and 2398 VEGF regulated genes were identified. Gene ontology analysis indicated that genes actively involved in uterus development were members of collagen biosynthesis, cell proliferation and cell apoptosis. Uterus-specific genes were enriched in activities of phosphatidyl inositol phosphate kinase, histone H3-K36 demethylation and protein acetylation. Among VEGF regulated genes, up-regulated genes were associated with RNA polymerase III activity while down-regulated genes were strongly associated with muscle development.Comparable numbers of antisense RNA transcripts were also identified. Expression levels of the antisense RNAs were found tightly correlated with their sense expression levels, an indication of possibly non-specific transcripts generated around the active promoters and enhancers. The antisense RNAs with exceptionally high or low expression levels and the antisense RNAs under VEGF regulation were also identified. These transcripts may be important candidates in regulation of uterus development. This study provides a global survey on genes and antisense transcripts regulated by VEGF in the pre-implantation stage. Results will contribute to the further studies of candidate genes and pathways in regulating implantation process and related diseases. Overall design: Uteri mRNA profiles of G2.5 VEGF-normal (Dox+) and VEGF-repression (Dox-) were generated by Solexa/ Illumina’s digital gene expression (DGE) system.

Publication Title

Transcriptional profiling of mouse uterus at pre-implantation stage under VEGF repression.

Sample Metadata Fields

Specimen part, Cell line, Subject

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accession-icon GSE81071
Gene expression from human discoid (DLE) and subacute (sCLE) cutaneous lupus subtypes
  • organism-icon Homo sapiens
  • sample-icon 56 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 2.1 ST Array (hugene21st)

Description

Cutaneous lupus erythematosus (CLE) is a disfiguring disease that can exist as an independent entity or as a manifestation of systemic lupus erythematosus (SLE) where up to 70% of patients experience lesions during their disease course. Subacute CLE (sCLE) is an inflammatory lesion with associated erythema in papulosquamous or annular formations. Typically, sCLE does not scar but depigmentation can occur. Importantly, sCLE is associated with a higher progression to SLE. Discoid lesions (DLE) are often circular and frequently lead to alopecia and scar formation. sCLE lesions have a higher propensity for photoprovocation and a more robust inflammatory infiltrate following ultraviolet (UV) B exposure. The pathogenic mechanisms which govern the differences between DLE and sCLE remain poorly defined, and this is reflected by the refractory nature of cutaneous lesions to usual lupus therapies. In this study, we evaluated the transcriptional profiles of 26 DLE and 23 sCLE biopsies and compared them to control skin and to each other in order to develop a comprehensive understanding of the similarities and differences between these two clinical subtypes.

Publication Title

Enhanced Inflammasome Activity in Systemic Lupus Erythematosus Is Mediated via Type I Interferon-Induced Up-Regulation of Interferon Regulatory Factor 1.

Sample Metadata Fields

Specimen part, Disease, Disease stage

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accession-icon SRP047000
Genome-wide analysis of whole transcriptome in E(z) temperature sensitive cells [RNA-Seq]
  • organism-icon Drosophila melanogaster
  • sample-icon 12 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000

Description

PcG protein complex PRC2 is a methyltransferase specific for histone H3 lysine27, and H3K27me3 is essential for stable transcription silencing. Less well known but quantitatively much more important is the genome-wide role of PRC2 that dimethylates ~70% of total H3K27. Here we show that H3K27me2 occurs in inverse proportion to transcriptional activity in genes and intergenic regions and its loss results in global transcriptional derepression proportionally greatest in previously silent or weakly transcribed regions. H3K27me2 levels are controlled by opposing roaming activities of PRC2 and the H3K27 demethylase dUTX. Unexpectedly, we find an equally pervasive distribution of histone H2A ubiquitylated at lysine 118 (H2AK118ub), attributed to the RING1 subunit of PRC1-type complexes. Overall design: Examination of global changes in transcription genome-wide when E(z) is inactivated by monitoring total RNA from E(z) temperature-sensitive cells at 25°C and 31°C in duplicate

Publication Title

Genome-wide activities of Polycomb complexes control pervasive transcription.

Sample Metadata Fields

Cell line, Subject

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accession-icon GSE28479
Maize gene expression during infection with Ustilago maydis strains SG200Dpit1 and SG200Dpit2
  • organism-icon Zea mays
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Maize Genome Array (maize)

Description

Ustilago maydis is a basidiomycete fungus that causes smut disease in maize. Most prominent symptoms of the disease are plant tumors, which can be induced by U. maydis on all aerial parts of the plant. We identified two linked genes, pit1 and pit2, which are specifically expressed during plant colonization. Deletion mutants for either pit1 or pit2 are unable to induce tumor development and elicit plant defense responses.

Publication Title

Two linked genes encoding a secreted effector and a membrane protein are essential for Ustilago maydis-induced tumour formation.

Sample Metadata Fields

Specimen part, Disease, Disease stage

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accession-icon GSE110531
Developmental and Functional Heterogeneity of White Adipocytes within a Single Fat Depot
  • organism-icon Mus musculus
  • sample-icon 23 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

We and others have previously observed that adipocytes and preadipocytes taken from different adipose tissue depots are characterized by differential expression of developmental and patterning genes (Dankel et al., 2010; Ferrer-Lorente et al., 2014; Gesta et al., 2006; Lee et al., 2017a; Lee et al., 2013; Macotela et al., 2012; Tchkonia et al., 2007; Yamamoto et al., 2010). To investigate how adipocyte heterogeneity and differences in the expression of developmental genes might impact the biology of adipocytes and preadipocytes, we created preadipocyte cell lines from the stromovascular fraction (SVF) isolated from the scapular white, inguinal, perigonadal, perirenal, and mesenteric fat pads of 6-week old male Immortomouse (Jat et al., 1991).During routine culture of the subcutaneous and visceral/perigonadal clonal cell lines, we observed extreme variation in media acidification rates that was unrelated to the fat pad of origin, the differentiation capacity of the cells, or the rate of their proliferation, suggesting metabolic heterogeneity. To further investigate this possibility, 24 clonal cell lines (12 each from subcutaneous and perigonadal fat) were selected based on variable media acidification rates, and their mRNA expression pattern determined by microarray analysis. The expression data was clustered using three different algorythms, and the consensus was used to categorize each type of adipose tissue.

Publication Title

Developmental and functional heterogeneity of white adipocytes within a single fat depot.

Sample Metadata Fields

Specimen part, Cell line

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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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