Single cell analysis revealed heterogeneous transcription factor profile of highly metastatic AFP-producing gastric cancer.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08363
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Nonaka Aya 東京大学, 先端科学技術研究センター, 特任研究員 (50786621)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: AFP産生胃がん / オルガノイド / 一細胞解析

Outline of Final Research Achievements

Alpha-fetoprotein producing gastric cancer (AFPGC) is a rare group of gastric cancers, but it frequently metastasizes to the liver and has a poor prognosis. However, AFPGC has been limited to immunostaining and case reports, and the mechanism of cancer development is poorly understood. In the present study, we identified the heterogeneity of AFPGC organoids established from clinical samples by single cell analysis. We observed that AFPGC organoids consist of two subpopulations differentiating into either hepatocyte-like or intestine-like cells in Wnt3a-free medium by single-cell RNA (scRNA) sequensing. Furthermore, by merging the data from single-cell ATAC and scRNA analysis, we identified that The enrichment rate of the HNF4A motif differs in the direction of differentiation. Differential expression of HNF4A isoforms may determine the direction of differentiation of AFPGC organoids.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究はこれまで免疫組織染色や症例報告などにとどまり、癌発生の機序はほとんど解明されていないAFPGCについて、一細胞解析を行うことによりその性質を明らかにした。AFPはAFPGCの腫瘍マーカーであるが、本研究でAFPGCの一部の細胞でしか発現が見られないことが明らかになった。またAFPGCの二方向性への分化は一つの転写因子のアイソフォームの発現差が関与していることが示され、AFPGCの発生機序解明への足掛かりになると考えられる。