Epigenetics regulation mechanisms in asymmetric division of brain tumor stem cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09393
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Saga University
• Principal Investigator: Nakahara Yukiko 佐賀大学, 医学部, 講師 (50380770)
• Co-Investigator(Kenkyū-buntansha): 阿部 竜也 佐賀大学, 医学部, 教授 (40281216) ; 伊藤 寛 佐賀大学, 医学部, 助教 (50795375)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: glioma / stem cell / asymmetric cell division

Outline of Final Research Achievements

Tumor stem cells exist in tumor tissues and adapt to various environments by balancing self-renewal and multilineage differentiation capacities through "asymmetric division," in which a single cell division generates the same tumor stem cell and highly differentiated cells. In this study, we used the IDH mutant stem cell line, which is an enzyme related to citrate metabolism, and the histone H3K27 mutant stem cell line to elucidate the mechanism of asymmetric division, which is the most distinctive feature of brain tumor stem cells. We examined differences in asymmetric division due to genetic differences in glioma stem cell lines and glioma patient-derived cell lines. Tumor stemness was quantified by specific gene expression. There were no differences in asymmetric division between the cell lines, and no correlation was demonstrated between differences in gene expression.

Free Research Field

脳腫瘍

Academic Significance and Societal Importance of the Research Achievements

我々は、腫瘍の代謝に関連するIDH遺伝子とエピゲノム異常の両者を橋渡す位置に存在するTETという分子に着目してきた。低酸素条件下でTET活性がさがりDNAメチル化によりがん抑制遺伝子の発現が低下する。DNAメチル化に加え抑制性ヒストン修飾であるH3K27me3が共存することで、強固な遺伝子不活機構として作用する。TETはES細胞において細胞分化関連遺伝子発現のON-OFFを担っており、ES細胞と同じ非対称性分裂能をもつ腫瘍幹細胞も同様の生存維持機構を有している可能性がある。腫瘍幹細胞の分裂機構を解明し、腫瘍幹細胞を分化誘導できれば、腫瘍組織の腫瘍幹細胞数を制御できる可能性がある。