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GSE39450
Gallus gallus
6 Downloadable Samples
Affymetrix Chicken Genome Array (chicken)
Description
Polycomb group proteins (PcG) are well known by their function in the regulation of developmental processes. PcG mediated regulation of genetic programs required for proper development are triggered by EZH2 H3K27 methyltransferase activity. EZH1 can partially substitute EZH2 activity. However, unlike EZH2, EZH1 is presence in differentiated and adult tissues suggesting additional biological functions. Here we show that EZH2 is predominantly expressed in neural stem cells being essential for neural stem cells self renewal and homeostasis. There, it controls the transcriptional state of cell cycle regulators, such as CIP1. But it is also necessary to regulate genes involved in surveillance and neuroepithelial polarity. In contrast, EZH1 expression is more abundant in differentiated cells within the spinal cord and its downregulation unables neural stem cells to differentiate. All together our data reveal a complementary but non-redundant role of EZH2 and EZH1 in neurogenesis.
Publication Title
EZH2 regulates neuroepithelium structure and neuroblast proliferation by repressing p21.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
Illumina HiSeq 2500
Description
Poised enhancers marked by H3K27me3 in pluripotent cells were previously proposed to facilitate the establishment of somatic expression programs upon embryonic stem cell (ESC) differentiation. However, the functional relevance and mechanism of action of poised enhancers remain unknown. Here, we use genetic deletions to demonstrate that poised enhancers are necessary for the induction of major anterior neural regulators. Mechanistically, poised enhancers enable RNA Polymerase II recruitment to their cognate promoters upon differentiation. Interestingly, poised enhancers already establish physical interactions with their target genes in ESC in a Polycomb repressive complex 2 (PRC2) dependent manner. Loss of PRC2 led to neither the activation of poised enhancers nor the induction of their putative target genes in undifferentiated ESC. In contrast, loss of PRC2 severely and specifically compromised the induction of major anterior neural genes representing poised enhancer targets. Overall, our work illuminates a novel function for polycomb proteins, which we propose facilitate neural induction by providing major anterior neural loci with a permissive regulatory topology. Overall design: mRNA profiles were generated by RNA-seq from mESC and AntNPC for the following lines: WT mESC, WT AntNPC, EED-/- mESC and EED-/- AntNPC
Publication Title
PRC2 Facilitates the Regulatory Topology Required for Poised Enhancer Function during Pluripotent Stem Cell Differentiation.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Poised enhancers marked by H3K27me3 in pluripotent cells were previously proposed to facilitate the establishment of somatic expression programs upon embryonic stem cell (ESC) differentiation. However, the functional relevance and mechanism of action of poised enhancers remain unknown. Here, we use genetic deletions to demonstrate that poised enhancers are necessary for the induction of major anterior neural regulators. Mechanistically, poised enhancers enable RNA Polymerase II recruitment to their cognate promoters upon differentiation. Interestingly, poised enhancers already establish physical interactions with their target genes in ESC in a Polycomb repressive complex 2 (PRC2) dependent manner. Loss of PRC2 led to neither the activation of poised enhancers nor the induction of their putative target genes in undifferentiated ESC. In contrast, loss of PRC2 severely and specifically compromised the induction of major anterior neural genes representing poised enhancer targets. Overall, our work illuminates a novel function for polycomb proteins, which we propose facilitate neural induction by providing major anterior neural loci with a permissive regulatory topology. Overall design: mRNA profiles were generated by RNA-seq from AntNPC derived from mESC: WT AntNPC (four biological replicates), PE Lhx5(-109)-/- Clon1 AntNPC (two biological replicates) and PE Lhx5(-109)-/- Clon2 AntNPC (two biological replicates).
Publication Title
PRC2 Facilitates the Regulatory Topology Required for Poised Enhancer Function during Pluripotent Stem Cell Differentiation.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The identification of inflammatory bowel disease (IBD) susceptibility genes by genome-wide association has linked this pathology to autophagy, a lysosomal degradation pathway that is crucial for cell and tissue homeostasis. Here, we describe autophagin-1 (ATG4B) as an essential protein in the control of inflammatory response during experimental colitis. In this pathological condition, ATG4B protein levels increase paralleling the induction of autophagy. Moreover, ATG4B expression is significantly reduced in affected areas of the colon from IBD patients. Consistently, atg4b-/- mice present Paneth cell abnormalities, as well as an increased susceptibility to DSS-induced colitis. Atg4b-deficient mice exhibit significant alterations in proinflammatory cytokines and mediators of the immune response to bacterial infections, which are reminiscent of those found in patients with Crohns disease or ulcerative colitis. Additionally, antibiotic treatments and bone marrow transplantation from wild-type mice reduced colitis in atg4b-/- mice. Taken together, these results provide additional evidence on the importance of autophagy in intestinal pathologies and describe ATG4B as a novel protective protein in inflammatory colitis. Finally, we propose that Atg4b-null mice are a suitable model for in vivo studies aimed at testing new therapeutic strategies for intestinal diseases associated with autophagy deficiency
Publication Title
ATG4B/autophagin-1 regulates intestinal homeostasis and protects mice from experimental colitis.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Transcriptional profiling of human acute myeloid leukemia cells lines HEL and SET2 transduced with an IGF1R shRNA and miR-125a sponge.
Publication Title
Loss of the proteostasis factor AIRAPL causes myeloid transformation by deregulating IGF-1 signaling.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The understanding of metastatic spread is limited and molecular mechanisms causing particular characteristics of metastasis, like varying dormancy periods of Mets originating from the same primary tumor entity or the differing number of Mets in patients with the same primary tumor, are largely unknown. Knowing the molecular fundamentals of these phenomena would support the prognosis of patients outcome and facilitate the decision for an appropriate therapy regime.
Publication Title
Gene signatures of pulmonary metastases of renal cell carcinoma reflect the disease-free interval and the number of metastases per patient.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
A large body of evidence has demonstrated that many human tumors are maintained by a small cell population called cancer stem cells (CSCs) or tumor progenitors, which are responsible for tumor formation, therapy resistance and metastasis. We found that ionizing radiation treatment enriches for the CSC phenotype and properties by preferential survival and expansion of tumor progenitor cells. Our studies revealed that aldehyde dehydrogenase (ALDH) activity is indicative of prostate tumor progenitor cells with increased chemo- and radioresistance, enhanced migratory potential, improved DNA- double strand break repair and activation of the signaling pathways, which promote self-renewal and epithelial-mesenchymal transition. We found that X-ray irradiation can convert the bulk tumor cells to more clonogenic and radioresistant population positive for expression of CSC markers. For the first time we showed that irradiation increases histone H3K4 and H3K36 methylation in prostate cancer cells, thereby reactivating transcription of epigenetically silenced target genes. We showed that radioresistant tumor progenitor population undergoes a phenotypical switching during the course of irradiation, suggesting that controlling the phenotypical and functional properties of CSCs during radiation therapy is ultimative for the optimization of treatment strategies. Our studies have shown that CSC markers may be beneficial in prediction of tumor radiocurability, and combination of irradiation with therapies directed against CSCs can be a useful strategy to improve cancer treatment.
Publication Title
Aldehyde Dehydrogenase Is Regulated by β-Catenin/TCF and Promotes Radioresistance in Prostate Cancer Progenitor Cells.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 107 Downloadable Samples
- Illumina ratRef-12 v1.0 expression beadchip
Description
Gene expression was analysed in the colon and brain of normal rat pups from late prenatal through early postnatal development. Tissue was isolated from pups one day prior to the anticipated date of birth and throughout the suckling period until the end of weaning.
Publication Title
Sialic acid utilisation and synthesis in the neonatal rat revisited.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 162 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
A gene expression profiling sub-study was conducted in which skin biopsy samples were collected from 85 patients with moderate-to-severe psoriasis who were participating in ACCEPT, an IRB-approved Phase 3, multicenter, randomized trial. This analysis identified 4,175 probe-sets as being significantly modulated in psoriasis lesions (LS) compared with matched biopsies of non-lesional (NL) skin.
Publication Title
Expanding the psoriasis disease profile: interrogation of the skin and serum of patients with moderate-to-severe psoriasis.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 49 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
There is a controversy surrounding the existence of palmoplantar pustulosis (PPP) and palmoplantar pustular psoriasis (PPPP) as separate clinical entities or as variants of the same clinical entity. We used gene expression microarray to compare gene expression in PPP and PPPP. PPP and PPPP could not be differentiated using gene expression microarray suggesting that they are not distinct clinical entities. Increased expression of GPRIN1, and ADAM23 in keratinocytes suggests that these proteins could be new therapeutic targets for PPP/PPPP.
Publication Title
Based on Molecular Profiling of Gene Expression, Palmoplantar Pustulosis and Palmoplantar Pustular Psoriasis Are Highly Related Diseases that Appear to Be Distinct from Psoriasis Vulgaris.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples