Epigenetic Regulation Mechanisms in Stress Hematopoiesis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08728
• 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: The University of Tokyo
• Principal Investigator: Nakajima-Takagi Yaeko 東京大学, 医科学研究所, 助教 (50749497)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: PRC1 / PCGF1 / Emergency myelopoiesis / GMP

Outline of Final Research Achievements

Polycomb group repressive complex (PRC) 1 regulates stem cell differentiation by mono-ubiquitination of H2AK119. In this study, we show that PRC1.1, a non-canonical PRC1, maintains the balance of hematopoietic cell differentiation at steady state by suppressing C/EBPa-dependent myeloid differentiation in HSPCs and the HOXA9-β-catenin self-renewing network in GMPs. On the other hand, transient inhibition of the HOXA9-β-catenin self-renewal network in the GMPs enhances GMP cluster formation and promotes emergency myelopoiesis. Our results define PRC1.1 as a novel critical regulator of emergency myelopoiesis, dysregulation of which leads to myeloid transformation.

Free Research Field

幹細胞分化

Academic Significance and Societal Importance of the Research Achievements

本研究によりPRC1.1は、定常時と緊急時の造血を調整し、骨髄細胞の悪性化を防ぐという重要な役割を担っていることが明らかとなった。このPRC1.1の新規機能の発見は、骨髄球系疾患の治療戦略として、PRC1.1を標的とすること、つまりPRC1.1の一時的な機能阻害を行うことで、緊急時造血を一過性に誘導し、骨髄球系細胞の供給力を高めるとともに、骨髄細胞の悪性化リスクを回避することができる新規のアプローチとしての応用の可能性を示すものである。