Filters
Technology
Platform
GSE90811
Homo sapiens
8 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Chronic low dose inorganic arsenic (iAs) exposure leads to changes in gene expression and epithelial-to-mesenchymal transformation. During this transformation, cells adopt a fibroblast-like phenotype accompanied by profound gene expression changes. While many mechanisms have been implicated in this transformation, studies that focus on the role of epigenetic alterations in this process are just emerging. DNA methylation controls gene expression in physiologic and pathologic states. Several studies show alterations in DNA methylation patterns in iAs-mediated pathogenesis, but these studies focused on single genes. We present a comprehensive genome-wide DNA methylation analysis using methyl-sequencing to measure changes between normal and iAs-transformed cells. Additionally, these differential methylation changes correlated positively with changes in gene expression and alternative splicing. Interestingly, most of these differentially methylated genes function in cell adhesion and communication pathways. To gain insight into how genomic DNA methylation patterns are regulated iAs-mediated carcinogenesis, we show that iAs probably targets CTCF binding at the promoter of DNA methyltransferases, regulating their expression. These findings reveal how transcription factor binding regulates DNA methyltransferase to reprogram the methylome in response to an environmental toxin.
Publication Title
Genome-wide DNA methylation reprogramming in response to inorganic arsenic links inhibition of CTCF binding, DNMT expression and cellular transformation.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
Illumina HiSeq 2500
Description
T follicular helper (TFH) cells promote affinity maturation of B cells in germinal centers (GCs), whereas T follicular regulatory (TFR) cells limit GC reaction. Store-operated Ca2+ entry (SOCE) through Ca2+ release-activated Ca2+ (CRAC) channels mediated by STIM and ORAI proteins is a fundamental signaling pathway in T lymphocytes. Here we show that SOCE is required for the differentiation and function of both TFH and TFR cells. Conditional deletion of Stim1 and Stim2 genes in T cells or Treg cells results in spontaneous autoantibody production and humoral autoimmunity. Conversely, antibody-mediated immune responses following viral infection critically depend on SOCE in TFH cells. Mechanistically, STIM1 and STIM2 control early TFR and TFH cell differentiation through NFAT-mediated IRF4, BATF and Bcl-6 expression. SOCE plays a dual role in GC response by controlling TFH and TFR cell function, thus enabling protective B cell responses and preventing humoral autoimmunity. Overall design: RNAseq analyses of WT and Stim1Stim2 DKO follicular T cells and non-follicular T cells; 4-6 mice per cohort in duplicates. Mice were infected for 10 days with LCMV.
Publication Title
Store-Operated Ca(2+) Entry in Follicular T Cells Controls Humoral Immune Responses and Autoimmunity.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To determine gene expression changes during in vitro senescence of MSC we have analyzed differential expression of the corresponding early passage (P2) and senescent passage (PX). There were global changes in the gene expression profile that were reproducible in three independent donor samples.
Publication Title
Replicative senescence of mesenchymal stem cells: a continuous and organized process.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In this series we have analyzed the effect of donor age on the gene expression profile of mesenchymal stromal cells (alternatively named mesenchymal stem cells; MSC) from human bone marrow. Cells were taken from bone marrow aspirates from iliac crest (BM) of healthy donors or from the caput femoris (HIP) of elderly patients that received femoral head prosthesis.
Publication Title
Aging and replicative senescence have related effects on human stem and progenitor cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 149 Downloadable Samples
- Illumina HiSeq 4000
Description
Diminishing potential to replace damaged tissues is a hallmark for ageing of somatic stem cells, but the mechanisms leading to ageing remain elusive. We present a proteome-wide atlas of age-associated alterations in human haematopoietic stem and progenitor cells (HPCs) along with five other cell types that constitute the bone marrow niche. For each, the abundance of a large fraction of the ~12,000 proteins identified was assessed in a cohort of healthy human subjects from different age. As the HPCs became older, pathways in central carbon metabolism exhibited features reminiscent of the Warburg effect where glycolytic intermediates are rerouted towards anabolism. Simultaneously, altered abundance of early regulators of HPC differentiation revealed a reduced functionality and a bias towards myeloid differentiation at the expense of lymphoid development. Ageing caused significant alterations in the bone marrow niche too, such as functionality of the pathways involved in HPC homing and lineage differentiation. The data represents a valuable resource for further in-depth mechanistic analyses, and for validation of knowledge gained from animal models. Overall design: RNA-seq samples extracted from human bone marrow, from 6 cell populations (HPC, LYM, MON, ERP, GRA, MSC). Technical replicates are included for each donor and cell type. Technical replicates were produced by making independent libraries from the same RNA.
Publication Title
Glycogen accumulation, central carbon metabolism, and aging of hematopoietic stem and progenitor cells.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Laser capture microdissected choroid plexuses were obtained and expression arrays were generated to investigate gene expression in wt and ApoE choroid plexuses; the choroid plexus forms the cerebrospinal fluid, the cerebrospinal fliod barrier, functions as the major gateway for blood-born leukocytes to enter the brain in degenerative and inflammatory brain diseases, and the principal neuroimmune interface in the brain. We found lipid deposits in the aged choroid plexus of hyperlipidemic mice but none in the wt control choroid plexuses. Here, we studied the functional impact and gene epressions in wt and ApoE-deficient choroid plexuses.
Publication Title
ApoE attenuates unresolvable inflammation by complex formation with activated C1q.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
A complex interplay between ethylene, ETP1/ETP2 F-box proteins, and degradation of EIN2 is essential for triggering ethylene responses in plants.
Publication Title
Interplay between ethylene, ETP1/ETP2 F-box proteins, and degradation of EIN2 triggers ethylene responses in Arabidopsis.
Sample Metadata Fields
Age, Treatment
View Samples- Homo sapiens
- 124 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Both cigarette smoking and obesity have been implicated in increased risk of clear cell renal cell carcinoma (ccRCC); however, there are limited data regarding the molecular mechanisms that underlie these associations. We used a multi-stage design to identify and validate specific molecular targets that are associated with smoking or obesity-related ccRCC.
Publication Title
ANKS1B is a smoking-related molecular alteration in clear cell renal cell carcinoma.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 73 Downloadable Samples
- Illumina HiSeq 2500
Description
The molecular regulation of zygotic genome activation (ZGA) in mammals remains poorly understood. Primed mouse embryonic stem cells contain a rare subset of “2C-like” cells that are epigenetically and transcriptionally similar to the two cell embryo and thus represent an ideal system for studying ZGA transcription regulation. Recently, the transcription factor Dux, expressed exclusively in the minor wave of ZGA, was described to activate many downstream ZGA transcripts. However, it remains unknown what upstream maternal factors initiate ZGA either in a Dux dependent or independent manner. Here we performed a candidate-based overexpression screen, identifying, amongst others, Developmental Pluripotency Associated 2 (Dppa2) and 4 (Dppa4) as positive regulators of 2C-like cells and ZGA transcription. In the germ line, promoter DNA demethylation coincides with upregulation of Dppa2 and Dppa4 which remain expressed until E7.5 when their promoters are remethylated. Furthermore, Dppa2 and Dppa4 are also expressed during iPSC reprogramming at the time 2C-like ZGA transcription transiently peaks. Through a combination of overexpression, knockdown, knockout and rescue experiments, together with transcriptional analyses, we show that Dppa2 and Dppa4 directly regulate the 2C-like cell population and associated transcripts, including Dux and the Zscan4 cluster. Importantly, we tease apart the molecular hierarchy in which the 2C-like transcriptional program is initiated and stabilised. Dppa2 and Dppa4 require Dux to initiate 2C-like ZGA transcription, suggesting they act upstream by directly regulating Dux. Supporting this, ChIP-seq analysis revealed Dppa2 and Dppa4 bind to the Dux promoter and gene body and drive its expression. Zscan4c is also able to induce 2C-like cells in wild type cells, but, in contrast to Dux, can no longer do so in Dppa2/4 double knockout cells, suggesting it may act to stabilise rather than drive the transcriptional network. Our findings suggest a model in which Dppa2/4 binding to the Dux promoter leads to Dux upregulation and activation of the 2C-like transcriptional program which is subsequently reinforced by Zscan4c. Overall design: RNA sequencing of screen hits (3 biological replicates of GFP+ and GFP- sorted cells for each of 12 candidates).
Publication Title
Dppa2 and Dppa4 directly regulate the Dux-driven zygotic transcriptional program.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 48 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The liver circadian clock is reprogrammed by nutritional challenge through the rewiring of specific transcriptional pathways. As the gut microbiota is tightly connected to host metabolism, whose coordination is governed by the circadian clock, we explored whether gut microbes influence circadian homeostasis and how they distally control the peripheral clock in the liver. Using fecal transplant procedures we reveal that, in response to high fat diet, the gut microbiota drives PPAR-mediated activation of newly oscillatory transcriptional programs in the liver. Moreover, antibiotics treatment prevents PPAR-driven transcription in the liver, underscoring the essential role of gut microbes in clock reprogramming and hepatic circadian homeostasis. Thus, a specific molecular signature characterizes the influence of the gut microbiome in the liver, leading to the transcriptional rewiring of hepatic metabolism.
Publication Title
Gut microbiota directs PPARγ-driven reprogramming of the liver circadian clock by nutritional challenge.
Sample Metadata Fields
Specimen part
View Samples