Speaker: Jing Xue, Stem Cell Center of Renji Hospital
Time: 10:00-11:00, 2024-11-29
Venue: A3-4-101
ZOOM: 388 528 9728
PW: BIMSA
Abstract
The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC) involves a significant accumulation of cancer-associated fibroblasts (CAFs) as part of the host response to tumor cells. The origins and functions of transcriptionally diverse CAF populations in PDAC remain poorly understood. Tumor cell-intrinsic genetic mutations and epigenetic dysregulation may reshape the TME; however, their impacts on CAF heterogeneity remains elusive. SETD2, a histone H3K36 trimethyl-transferase, functions as a tumor suppressor. Through single-cell RNA sequencing, we identify a novel lipid-laden CAF subpopulation marked by ABCA8a in Setd2-deficient pancreatic tumors. Our findings reveal that tumor-intrinsic SETD2 loss unleashes BMP2 signaling via ectopic gain of H3K27Ac, leading to CAFs differentiation towards lipid-rich phenotype. Lipid-laden CAFs then enhance tumor progression by providing lipids for mitochondrial oxidative phosphorylation via ABCA8a transporter. Together, our study links CAF heterogeneity to epigenetic dysregulation in tumor cells, highlighting a previously unappreciated metabolic interaction between CAFs and pancreatic tumor cells.
Speaker Intro
Dr. Xue Jing is currently serving as a researcher and doctoral supervisor at the Stem Cell Center of Renji Hospital, Shanghai Jiao Tong University School of Medicine, and the National Laboratory of Systems Medicine for Cancer. She completed her doctoral degree in June 2010 from the Institute of Nutrition Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. In October 2010, Dr. Xue pursued postdoctoral research at the School of Medicine, Stanford University in the United States. In September 2015, she returned to China and joined Shanghai Jiao Tong University School of Medicine. Her research group primarily focuses on pancreatic tumors and inflammation, delving into related pathological mechanisms from aspects such as immune regulation and epigenetic regulation. In recent years, Dr. Xue's research findings have been published in prestigious journals including Cancer Cell, Gut, Gastroenterology, Advanced Science, and Cancer Research. She has received funding from National Natural Science Foundation of China, including General program and Excellent Young Scientist Fund, as well as the Shanghai Eastern Scholar and the Shanghai Youth Talent Program.
