Project description:EZH2 plays an important role in stem cell renewal and maintenance by inducing gene silencing via its histone methyltransferase activity. Previously, we showed EZH2 downregulation markedly enhances neuron differentiation of human mesenchymal stem cells (hMSCs). To understand how EZH2 regulates neuron differentiation of hMSCs, we wanted to identify the target genes of EZH2. For this reasons we performed ChIP-on-chip experiments using specific EZH2 antibodies followed by a human promoter array for the whole human genome. The 3A6-hMSCs were differentiated into neuron for 5 days, and then 109 cells were harvested for the ChIP-on-chip assay. The procedure was based on the manufacturer's instructions (NimbleGen).
Project description:EZH2 plays an important role in stem cell renewal and maintenance by inducing gene silencing via its histone methyltransferase activity. Previously, we showed EZH2 downregulation markedly enhances neuron differentiation of human mesenchymal stem cells (hMSCs). To understand how EZH2 regulates neuron differentiation of hMSCs, we wanted to identify the target genes of EZH2. For this reasons we performed ChIP-on-chip experiments using specific EZH2 antibodies followed by a human promoter array for the whole human genome.
Project description:EZH2 plays an important role in stem cell renewal and maintenance by inducing gene silencing via its histone methyltransferase activity. EZH2 downregulation markedly enhances neuron differentiation of human mesenchymal stem cells (hMSCs)chromatin at promoters of EZH2 target genes. comparison of knockdown EZH2 of hMSCs vs hMSCs
Project description:EZH2 plays an important role in stem cell renewal and maintenance by inducing gene silencing via its histone methyltransferase activity. EZH2 downregulation markedly enhances neuron differentiation of human mesenchymal stem cells (hMSCs)chromatin at promoters of EZH2 target genes.
Project description:<p>BRCA1 mutations are a hallmark of hereditary ovarian cancer, strongly linked to deficiencies in homologous recombination (HR) DNA repair and impaired DNA replication fork protection. However, its roles in cancer progression beyond maintaining genomic integrity remain poorly understood. Through metabolomics approaches, we found BRCA1-deficiency strikingly increased choline metabolism. Loss of BRCA1 promotes choline uptake through upregulating choline transporter-like protein 4 (CTL4). BRCA1 directly binds and recruits EZH2-mediated H3K27Me3 deposition to CTL4 promoter. CTL4 was therefore overexpressed in ovarian cancer tissues with BRCA1 mutations. Furthermore, BRCA1-deficiency significantly promotes ovarian cancer invasion, while inhibition of CTL4 reverses the high metastatic potential of BRCA1-deficient ovarian cancer cells, suggesting the functionality and specificity of CTL4 as a therapeutic target. Additionally, we discovered that phosphocholine, the choline metabolite increased by CTL4 overexpression, interacted with and stabilized the epithelial-to-mesenchymal transition inducer FAM3C in BRCA1-deficient ovarian cancer cells. Importantly, we identified a potent CTL4 inhibitor, DT-13, which significantly reduces choline metabolism and effectively suppresses metastasis in BRCA1-deficient ovarian cancers. Therefore, our study uncovers a mechanism underlying metastasis in BRCA1-deficient cancers and identifies CTL4 as a therapeutic target for metastatic ovarian cancer patients with BRCA1 mutations.</p>
Project description:Long non-coding RNAs profiling of human mesenchymal stem cells comparing undifferentiated HMSCs with differentiated HMSCs during chondrogenesis. The chondrogenic differentiation of HMSCs was induced by chondrogenic medium. The chondrogenic marker genes (Col2a1, Sox9 and ACAN) has been detected upregulating during this process by Q-PCR. The aim of this study is to determine key lncRNAs regulating the chondrogenic differentiation process.