Project description:The aim of the experiment was to gain insight into the role of estrogen receptor beta (ERβ) isoforms in the response of breast cancer MCF7 cells to antiestrogens and retinoids. To this end, clones of MCF7 cells constitutively expressing human ERβ1 (MCF7-ERβ1) or ERβ2 (MCF7-ERβ2) were established and used for the determination of the global transcriptional changes induced upon treatment with hydroxytamoxifen (OHT) and all-trans retinoic acid (ATRA). Gene signatures associated with each clone will shed light to the mechanism underlying the ERβ1- and ERβ2-mediated response of MCF7 cells to antiestrogens and retinoids.
Project description:We investigated the cell identity and cell proportion in the intestinal organoids treated by Isoxazole-9 (Isx-9) using single-cell transcriptome analysis. Isx-9 enriches enteroendocrine cells without altering the cell identity of other lineages. To investigate the mechanism of this process, we performed RNA-seq and ATAC-seq of Isx-9 treated intestinal stem cells. Based on the gene expression pattern and differential peaks of open chromatin, we found that Isx-9 upregulated neuroendocrine related genes, and elevated the chromatin accessibility at the promoter region of enteroendocrine related transcription factors.
Project description:We developed a strategy to generate cardiac progenitor cells from human induced pluripotent stem cells using a novel small molecule. mRNA-sequencing results showed different gene expression profile among undifferentiated human induced pluripotent stem cells(hiPSCs), DMSO and ISX-9 treated hiPSCs.In comparsion with DMSO treated cells or undifferentiated hiPSCs, ISX-9 upregulated the genes related to WNT and cytoskeleton remodeling and TGF-β signaling, which are involved in heart development and cardiac differentiation. In addition, the genes related to cardiac differentiation signaling pathways were upregulated by ISX-9 including development of PIP3 signaling in cardiomyocyte myocytes, muscle contraction and NF-AT hypertrophy signaling.
Project description:We developed a strategy to generate cardiac progenitor cells from human induced pluripotent stem cells using a novel small molecule.miRNA-sequencing results showed different miRNA expression profile among undifferentiated human induced pluripotent stem cells(hiPSCs), DMSO and ISX-9 treated hiPSCs.In comparsion with DMSO treated cells, ISX-9 upregulated several myogenic miRNAs and cardiac hypertrophy related-miRNAs including miR-335, miR-21, miR-30c,miRNA-181a and miR-214.
Project description:The tumor suppressor p53 can induce various biological responses. Yet it is not clear whether it is p53 in vivo promoter selectivity that triggers different transcription programs leading to different outcomes. Our analysis of genome-wide chromatin occupancy by p53 using ChIP-seq (deposited in Sequence Read Archive database as SRP007261) revealed “p53 default program”, i.e. the pattern of major p53-bound sites that is similar upon p53 activation by nutlin3a, RITA or 5-FU in breast cancer cells, despite different biological outcomes triggered by these compounds. Parallel analysis of gene expression allowed identification of 280 previously unknown p53 target genes, including p53-repressed AURKA. The consensus p53 binding motif was present more frequently in p53-induced, than in repressed targets, indicating different mechanisms of gene activation versus repression. We identified several possible cofactors of p53, and found that STAT3 antagonised p53-mediated repression of a subset of genes, including AURKA. Finally, we showed that the expression of the novel p53 targets correlates with p53 status and survival in breast cancer patients. We used microarrays to detail the global programme of gene expression changed upon nutlin3a treatment and knocking-down of STAT3 transcription program MCF7 cell with or without knock-down of STAT3 were treated with nutlin3a and collected for RNA extraction and hybridization on Affymetrix microarrays.