学术讲座：Lineage-specific Transcription Factors suppress activation of Hepatic Stellate Cells during Liver Fibrosis

讲座内容简介：

Liver fibrosis induced by hepatocyte injury results from the activation of quiescent Hepatic Stellate Cells (qHSCs) into Collagen Type I-producing myofibroblasts (aHSCs). Resolution of fibrosis is associated with inactivation of about 50% aHSCs/myofibroblasts into a quiescent-like phenotype (iHSCs). To identify the molecular drivers of these HSC states, we investigated the global epigenetic changes in H3K4me2 and H3K27ac chromatin marks in qHSCs, aHSCs, and iHSCs. Motif enrichement and gene expression analysis identified ETS1/2, GATA4/6, and IRF1/2 transcription factors (TFs) as putative lineage regulators of the quiescent/inactivated HSC state. In vitro shRNA-knockdown of each TF and HSC-specific genetic ablation of GATA6 or the ETS1 target genes NF1 and PPARγin vivo confirmed the essential roles of these genes in HSC quiescence and inactivation in mice. Similar mechanisms were active in human HSCs, suggesting that inactivation of aHSCs/myofibroblasts into a quiescent-like state may serve as a novel strategy to halt liver fibrosis in humans.

报告人：

刘骁，药理学硕士，毕业于美国俄勒冈州立大学，现为美国加州大学圣地亚哥分校，医学院肝胆肠道科，高级助理研究员。主要研究方向是利用人原代细胞结合小鼠体内体外模型来研究肝星状细胞在肝硬化过程中的调控机制，并以肝星状细胞为靶点来研发肝纤维化创新药物。

时间：2019年3月8日 上午9:30-10-30

地点：426报告厅