Background: The heteroplasmic mitochondrial DNA (mtDNA) mutation A3243G causes the MELAS syndrome as one of the most frequent mitochondrial diseases. The process of reconfiguration of nuclear gene expression profile to accommodate cellular processes to the functional status of mitochondria might be a key to MELAS disease manifestation and could contribute to its diverse phenotypic presentation.
No associated publication
Sex, Specimen part, Subject
View SamplesProliferation of the self-renewing epithelium of the gastric corpus occurs almost exclusively in the isthmus of the glands, from where cells migrate bi-directionally towards pit and base. The isthmus is therefore generally viewed as the stem cell zone. We find that the stem cell marker Troy is expressed at the gland base by a small subpopulation of chief cells. By lineage tracing using a Troy-eGFP-ires-CreERT2 allele, single marked cells are shown to generate entirely labeled gastric units over periods of months. This phenomenon accelerates upon tissue damage. Troy+ chief cells can be cultured to generate long-lived gastric organoids. Troy marks a specific, 'plastic' subset of differentiated chief cells capable of replenishing entire gastric units, essentially serving as a quiescent reserve stem cell.
Differentiated Troy+ chief cells act as reserve stem cells to generate all lineages of the stomach epithelium.
Specimen part
View SamplesTranscriptome analysis of murine foetal NSCs (E14) after short-term (48 hours) and long-term (13 days) hypoxic (3% oxygen) culture compared to normoxic culture (21% oxygen)
No associated publication
Specimen part
View SamplesFetal liver of E14.5 RNaseh2b KOF and Rnaseh2b wild type embryos was isolated, RNA was extracted and microarray analysis using Affymetrix Mouse 430 2.0 gene chip was performed
Mammalian RNase H2 removes ribonucleotides from DNA to maintain genome integrity.
Specimen part
View SamplesPHD4 regulates the expression of Hypxia-inducible Factor 2 (HIF-2) alpha in LM8 osteosarcoma cells. PHD4 overexpression inhibits the growth of experimental tumor in syngenic mice but stimulates angiogenesis via Transforming Growth-Factor (TGF)-alpha.
PHD4 stimulates tumor angiogenesis in osteosarcoma cells via TGF-α.
Cell line, Treatment
View SamplesEmbryonic stem cells (ESCs) cells run a self-renewal gene expression program, requiring the expression of certain transcription factors accompanied by a particular chromosome organization to maintain a balance between pluripotency and the capacity for rapid differentiation. However, how transcriptional regulation is linked to chromosome organization in ESCs remains enigmatic. Here we show that Cohesin exhibits a functional role in maintaining ESC identity through association with the pluripotency transcriptional network. ChIP-seq analyses of the cohesin subunit Rad21 reveal an ESC specific cohesin binding pattern that is characterized by a CTCF independent colocalization of cohesin with pluripotency related transcription factors. Upon ESC differentiation, these binding sites disappear and instead new CTCF independent Rad21 binding sites emerge, which are enriched for binding sites of transcription factors implicated in early differentiation. Furthermore, knock-down of cohesin subunits causes expression changes that are reminiscent of the depletion of key pluripotency transcription factors, demonstrating the functional relevance of the cohesin - pluripotency transcriptional network association. Finally, we show that Nanog physically interacts with the cohesin interacting proteins Stag1 and Wapl, further substantiating this association. Based on these findings we propose that a dynamic placement of cohesin by pluripotency transcription factors contributes to a chromosome organization supporting the ESC expression program.
RAD21 cooperates with pluripotency transcription factors in the maintenance of embryonic stem cell identity.
Specimen part
View SamplesThe Cohesin complex has recently been described to regulate gene expression. We wanted to determine the gene expression profile specific in mouse ES cells after depletion of the Cohesin subunit Rad21.
No associated publication
Specimen part
View SamplesLong non-coding RNAs (lncRNAs) regulate diverse biological pathways. Unlike protein coding genes, where methods to comprehensibly study their functional roles in cellular systems are available, techniques to systematically investigate lncRNAs have largely remained unexplored. Here, we report a technology for combined Knockdown and Localization Analysis of Non-coding RNAs (c-KLAN) that merges phenotypic characterization and localization approaches to study lncRNAs. Using a library of endoribonuclease prepared short interfering RNAs (esiRNAs) coupled with a pipeline for synthesizing labeled riboprobes for RNA fluorescence in situ hybridization (FISH), we demonstrate the utility of c-KLAN by identifying a novel transcript Panct1 (Pluripotency associated non-coding transcript 1) that regulates embryonic stem cell identity. We postulate that c-KLAN should be generally useful in the discovery of lncRNAs implicated in various biological processes.
Combined RNAi and localization for functionally dissecting long noncoding RNAs.
Specimen part
View SamplesThe understanding of metastatic spread is limited and molecular mechanisms causing particular characteristics of metastasis are largely unknown. This comprises the extremely varying dormancy periods of tumor cells in the secondary organ after metastatic spread, represented by the disease-free survival (DFS) of the patients, or differing numbers of metastases in different patients. Knowing the molecular fundamentals of these phenomena would support the individual prediction of patients outcome and facilitate the decision for an appropriate monitoring and therapy regime.
CD31, EDNRB and TSPAN7 are promising prognostic markers in clear-cell renal cell carcinoma revealed by genome-wide expression analyses of primary tumors and metastases.
Sex, Specimen part, Disease stage
View SamplesThe 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.
Gene signatures of pulmonary metastases of renal cell carcinoma reflect the disease-free interval and the number of metastases per patient.
Sex
View Samples