Crosstalk between chromosome modification and transcription factors in the differentiation of hematopoietic cells

2014 Fiscal Year Final Research Report

• Project Area: Molecular mechanisms of cell fate determination in the cells that undergo stepwise differentiation to multiple pathways
• Project/Area Number: 22118002
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: KITAMURA Toshio 東京大学, 医科学研究所, 教授 (20282527)
• Co-Investigator(Kenkyū-buntansha): SAKAUE Asako 独立行政法人理化学研究所, 脳科学総合研究センター, 研究員 (90462689) ; YAMAMOTO Masayuki 東北大学, 医学(系)研究科(研究院), 教授 (50166823)
• Co-Investigator(Renkei-kenkyūsha): ISHIKAWA Fumihiko 独立行政法人理化学研究所, その他部局等, ユニットリーダー (30403918) ; MIYAWAKI Atsushi 独立行政法人理化学研究所, 脳科学総合研究センター, チームリーダー (80251445)
• Project Period (FY): 2010-04-01 – 2015-03-31
• Keywords: 細胞分化 / エピジェネティクス / 細胞周期

Outline of Final Research Achievements

We have demonstrated that the mutation of ASXL1 an epigenetic factor induces a myelodysplastic syndromes-like disease in mouse using mouse bone marrow transplant models. Concerning the molecular mechanisms, we have identified that suppression of PRC2 functions lead to derepression of HoxA9 and miR125a, playing critical roles in cell transformation and suppression of cell differentiation. In addition, we have identified a series of ASXL1 binding proteins, and investigate the physiological roles of ASXL1 in normal hematopoiesis. We also developed a novel G0 marker which expresses mVenus fluorescent protein only in cells in the G0 phase. We have now established and started the characterization of the transgenic mice expressing this G0 marker in hematopoietic cells.

Free Research Field

血液学