Title: Circadian clock and liver polyploidization

Speaker: Assistant Professor Hsu-wen Chao (Taipei Medical University, China)

Time: 2:30-4:00pm, March 14th, 2018

Venue: Room No. 4129, Lecture Hall, Building 4, North Campus, College of Veterinary Medicine

Abstract:

Liver metabolism undergoes robust circadian oscillations in gene expression and enzymatic activity essential for liver homeostasis, but whether the circadian clock controls homeostatic self-renewal of hepatocytes is unknown. Here we show that hepatocyte polyploidization is markedly accelerated around the central vein, the site of permanent cell self-renewal, in mice deficient in circadian Period genes. In these mice, a massive accumulation of hyperpolyploid mononuclear and binuclear hepatocytes occurs due to impaired mitogen-activated protein kinase phosphatase 1 (Mkp1)-mediated circadian modulation of the extracellular signal regulated kinase (Erk1/2) activity. Time-lapse imaging of hepatocytes suggests that the reduced activity of Erk1/2 in the midbody during cytokinesis results in abscission failure, leading to polyploidization. Manipulation of Mkp1 phosphatase activity is sufficient to change the ploidy level of hepatocytes. These data provide clear evidence that the Period genes not only orchestrate dynamic changes in metabolic activity, but also regulate homeostatic selfrenewal of hepatocytes through Mkp1-Erk1/2 signaling pathway.

A Brief Introduction to the Speaker:

Dr. Hsu-wen Chao graduated and acquired his Ph.D degree from Institute of Biomedical Science, Academia Sinica, Taiwan, China in 2010. From 2016 to the present, He was an assistant professor of Department of Physiology, School of Medicine, Taipei Medical University. Dr. Chao published 8 papers in famous international academic journals, such as Journal of Cell Biology, Journal of Clinical Investigation, Nucleic Acids Research, Nature communications, Cell Reports, Journal of Neuroscience.

All the teachers and students are welcome to attend this seminar.

College of Veterinary Medicine

March 10th, 2018