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GSE66534
Mus musculus
9 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The histone chaperone CAF-1 safeguards somatic cell identity.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Cellular differentiation involves profound changes in the chromatic landscape, yet the mechanisms by which somatic cell identity is subsequently maintained remain incompletely understood. To further elucidate regulatory pathways that safeguard the somatic state, we performed two comprehensive RNAi screens targeting chromatin factors during transcription factor-mediated reprogramming of mouse fibroblasts to induced pluripotent stem cells (iPSCs). Remarkably, subunits of the chromatin assembly factor-1 (CAF-1) complex emerged as the most prominent hits from both screens, followed by modulators of lysine sumoylation and heterochromatin maintenance. Suppression of CAF-1 increased reprogramming efficiency by several orders of magnitude and facilitated iPSC formation in as little as 4 days. Mechanistically, CAF-1 suppression led to a more accessible chromatin structure at enhancer elements early during reprogramming. These changes were accompanied by a decrease in somatic heterochromatin domains, increased binding of Sox2 to pluripotency-specific targets and activation of associated genes. Notably, suppression of CAF-1 also enhanced the direct conversion of B cells into macrophages and fibroblasts into neurons. Together, our findings reveal the histone chaperone CAF-1 as a novel regulator of somatic cell identity during transcription factor-induced cell fate transitions and provide a potential strategy to modulate cellular plasticity in a regenerative setting.
Publication Title
The histone chaperone CAF-1 safeguards somatic cell identity.
Sample Metadata Fields
Specimen part, Time
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
Elevated fructose consumption has been associated with metabolic and renal diseases. It is controversial whether kidney problems are a result of systemic metabolic disease or stem, at least in part, from changes due to local fructose metabolism. To study the short-term effect of fructose on genetic programs in renal proximal tubules, the diet for rats in experimental groups was supplemented for 7 days with 20% fructose in the drinking water. Two sets of 8 rats each on different baseline rodent diets were used in this study. 4 animals of each set received fructose in the drinking water while the other 4 served as controls. Animals were sacrificed after the experimental period of 7 days and slices of superficial kidney cortex were used for total RNA extraction. The RNA was analyzed with Affymetrix RaGene-2_0-st.
Publication Title
Transcriptome signature for dietary fructose-specific changes in rat renal cortex: A quantitative approach to physiological relevance.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 50 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Purpose:
Publication Title
Sequential gene expression profiling during treatment for identification of predictive markers and novel therapeutic targets in chronic lymphocytic leukemia.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The human hair follicle bulge is an important niche for keratinocyte stem cells (KSC). Elucidation of human bulge cell biology could be facilitated by analysis of global gene expression profiles and identification of unique cell surface markers. The lack of distinctive bulge morphology in human hair follicles has hampered studies of bulge cells and KSC. In this study, we determined the distribution of label-retaining cells to carefully define the human anagen bulge. Using navigated-laser capture microdissection, bulge cells and outer root sheath cells from other follicle regions were obtained and analyzed with cDNA microarrays. Gene transcripts encoding inhibitors of WNT and Activin/BMP signaling were over-represented in the bulge while genes responsible for cell proliferation were under-represented, consistent with quiescent non-cycling KSC in anagen follicles. Positive markers for bulge cells included CD200, PHLDA1, follistatin, and frizzled homolog 1 while CD24, 34, 71 and 146 were preferentially expressed by non-bulge keratinocytes. Importantly, CD200+ cells (CD200hi24lo34lo71lo146lo) obtained from hair follicle suspensions demonstrated high colony forming efficiency in clonogenic assays, indicating successful enrichment of living human bulge stem cells.
Publication Title
Characterization and isolation of stem cell-enriched human hair follicle bulge cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Autosomal recessive polycystic kidney disease is a severe, monogenetically inherited kidney and liver disease and PCK rats carrying the orthologous mutant gene serve as a model of human disease. We combined selective MALDI imaging of sulfated kidney lipids and Fisher discriminant analysis of imaging data sets for identification of candidate lipid markers of progressive disease in PCK rats. Our study highlights strong increases in lower mass lipids as main classifiers of cystic disease. Structure determination by high resolution mass spectrometry identifies these altered lipids as taurine-conjugated bile acids. Beside increased levels of serum-cholesterol these sulfated lipids are selectively elevated in the PCK rat model but not in models of related hepatorenal fibrocystic diseases suggesting that they be molecular markers of the disease.
Publication Title
MALDI imaging MS reveals candidate lipid markers of polycystic kidney disease.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 18 Downloadable Samples
Illumina HiSeq 2500
Description
For Samples 1-8 and 11-18: The innate immune sensor retinoic acid-inducible gene-I (RIG-I) detects double-stranded RNA derived from RNA viruses, and recent studies have demonstrated that RIG-I also plays a role in the antiviral response to DNA viruses. To identify the physiological RNA species that are recognized by RIG-I during HSV-1 infection, we purified the RNAs that co-immunoprecipitated with FLAG-tagged RIG-I in transfected human embryonic kidney (HEK) 293T cells that had been infected with a recombinant HSV-1 (hereafter referred to as HSV-1 mut) containing a mutation (K220A) in the viral serine/threonine protein kinase US3 that abolishes its catalytic activity, as the viral kinase is known to antagonize type-I IFN responses. As controls, RNA species bound to FLAG-RIG-I in uninfected cells and RNA bound to FLAG-GFP from both HSV-1 mut-infected and uninfected cells were also purified. RIG-I-bound RNA and total RNA extracted from uninfected and HSV-1 mut-infected cells were analyzed by RNAseq, and the resulting sequences were mapped to both the HSV-1F-strain and human genome (hg38). This analysis revealed that several human transcripts were highly enriched in the RIG-I-bound fraction from infected cells; in contrast, the enrichment of viral sequences was low. The cellular transcripts that were most abundant in the RIG-I fraction were predominantly non-coding RNAs from different subclasses, as well as some coding RNAs. For Samples 9 and 10: HSV-1 infection is known to induces changes in the transcriptional profile of the infected cell. To analyze global changes in RNA transcript levels in infected cells, total RNA was extracted from HEK 293T cells that were infected with wild-type (WT) HSV-1. For comparison, total RNA was extracted from HEK 293T cells that remained uninfected. Next, RNAseq analysis was performed. The resulting sequences were mapped to the human genome, and gene inductions were calculated and normalized to uninfected samples to determine changes in gene expression upon infection. Overall design: Cells, which were not infected or infected with either wildtype HSV-1 or mutated HSV-1 were either subjected to a pulldown isolating RLR/GFP associated RNA (8 samples) or the corresponding total RNA (8 samples) was extracted from the infected cells and sequenced. Additionally, non-transfected cells were infected and total RNA extracted and sequenced (2 samples)
Publication Title
Viral unmasking of cellular 5S rRNA pseudogene transcripts induces RIG-I-mediated immunity.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Saccharomyces cerevisiae
- 36 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
tRNAs are transcribed and partially processed in the nucleus before they are exported to the cytoplasm where they have an essential role in protein synthesis. Surprisingly, mature cytoplasmic tRNAs shuttle between nucleus and cytoplasm and its distribution is nutrient-dependent. At least three members of -importin family, Los1, Mtr10, and Msn5, function in tRNA nuclear-cytoplasmic intracellular movement. To test the hypothesis that the tRNA retrograde pathway regulates translation of particular transcripts
Publication Title
Genome-wide investigation of the role of the tRNA nuclear-cytoplasmic trafficking pathway in regulation of the yeast Saccharomyces cerevisiae transcriptome and proteome.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
T-cell prolymphocytic leukemia (T-PLL) is a rare and poor-prognostic mature T-cell malignancy. To address its incomplete molecular concept, we integrated large-scale profiling data of alterations in gene expression, allelic copy number (CN), and nucleotide sequences in 111 well-characterized patients. Besides prominent signatures of T-cell activation and prevalent clonal variants, we also identified novel hot-spots for CN variability, fusion molecules, alternative transcripts, and progression-associated dynamics. The overall lesional spectrum of T-PLL is mainly annotated to axes of DNA damage responses, T-cell receptor / cytokine signaling, and histone modulation. We formulate a multi-dimensional model of T-PLL pathogenesis centered around a unique combination of TCL1 overexpression with damaging ATM aberrations as initiating core lesions. The effects imposed by TCL1 cooperate with compromised ATM towards a leukemogenic phenotype of impaired DNA damage processing. Dysfunctional ATM appears inefficient in alleviating elevated redox burdens and telomere attrition and in evoking a p53-dependent apoptotic response to genotoxic insults. As non-genotoxic strategies, synergistic combinations of p53 reactivators and deacetylase inhibitors reinstate such cell death execution.
Publication Title
Actionable perturbations of damage responses by TCL1/ATM and epigenetic lesions form the basis of T-PLL.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We assessed vastus lateralis muscle gene expression levels of 12 women with the metabolic syndrome before and after a 6 month exercise training program
Publication Title
Upregulation of skeletal muscle inflammatory genes links inflammation with insulin resistance in women with the metabolic syndrome.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage, Treatment, Subject, Time
View Samples