Regulation of cancer specific chromatin and transcriptional network by Hmga2

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08842
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Kumamoto University
• Principal Investigator: Yokomizo Takako 熊本大学, 国際先端医学研究機構, 特定事業研究員 (40636867)
• Co-Investigator(Kenkyū-buntansha): 白 潔 熊本大学, 国際先端医学研究機構, 外国人客員研究員 (60775336)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: Hmga2 / 造血幹細胞

Outline of Final Research Achievements

High Mobility Group AT-hook 2 (HMGA2) is a chromatin modifier and the expression levels of Hmga2 were found to be markedly higher in fetal HSCs than in adult HSCs. Furthermore, overexpression of Hmga2 has been found in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Although Hmga2 had been known to enhance the self-renewal capacity of HSCs, the molecular mechanism of how Hmga2 regulates chromatin complexes of normal HSC and MDS-stem cells is still unclear. In this study, we showed Hmga2 directly activated Igf2bp2 to enhance the self-renew of HSC, but also repressed the inflammatory response to protect HSC from damage in the stress condition. Hmga2 may regulate transcriptional program to maintain normal hematopoiesis and regeneration in the response to environmental stress.

Free Research Field

造血幹細胞

Academic Significance and Societal Importance of the Research Achievements

Hmga2は胎児造血幹細胞の高い自己複製機能に必須の因子であるほか、骨髄異形成症候群（MDS）や急性骨髄性白血病（AML）においてがん遺伝子としての機能も示唆されている。本研究では、成体造血においてHmga2がストレス状況下で造血幹細胞を障害から守り、造血の維持と再生に寄与するという新たなHmga2の機能を示した。本研究成果は、老化造血幹細胞の若返りや、がん幹細胞の維持機構を理解する上で意義深いものと考える。