Project description:Orchestrated actions of tissue-specific enhancers and transcription factors (TFs) govern the development of the placenta which is an essential organ to support the growth of the fetus during pregnancy. However, human trophoblast stem cells (TSCs)-specific enhancers, TFs, and the mechanisms by which TFs modulate placental development are poorly understood. Here we investigated enhancers, super-enhancers (SE), SE-associated genes in human TSC using RNA-seq and ChIP-seq to interrogate the roles of SE-TFs in human TSCs.
Project description:Orchestrated actions of tissue-specific enhancers and transcription factors (TFs) govern the development of the placenta which is an essential organ to support the growth of the fetus during pregnancy. However, human trophoblast stem cells (TSCs)-specific enhancers, TFs, and the mechanisms by which TFs modulate placental development are poorly understood. Here we investigated enhancers, super-enhancers (SE), SE-associated genes in human TSC using RNA-seq and ChIP-seq to interrogate the roles of SE-TFs in human TSCs.
Project description:Chromatin organisation of trophoblast stem cells (TSC) were compared with that of embryonic stem cells (ESC). The method enriches Hi-C libraries, to detect promoter interactions at restriction fragment level. We prepared Hi-C libraries from TSC and ESC (serum grown) samples and enriched them with a promoter capture bait system that captures ~22.000 promoters. Promoter interactions were then analysed using the GOTHiC pipeline.
Project description:Treatment resistant epilepsy in tuberous sclerosis complex (TSC) and some focal cortical dysplasias (FCDs) are associated with dysfunctional mammalian target of rapamycin (mTOR) signaling. This can upregulate cell growth and proliferation, with increased downstream ribosomal S6 protein phosphorylation (phospho-S6). mTOR inhibitors are used in TSC, the archetypal mTORopathy, to reduce tumor growth or seizure frequency. Preclinical studies in FCD support a potential role in suppressing seizures. This pilot study sought to evaluate the safety of the mTOR inhibitor everolimus in treatment-resistant (failure of > 2 anti-seizure medications) TSC and FCD patients undergoing surgical resection and to assess changes in mTOR signaling and molecular pathways.
Project description:Unraveling the functional role of DNA demethylation at specific promoters by targeted steric blockage of DNA methyltansferase with CRISPR/dCas9