Development of novel therapeutic strategy against myeloid leukemia by inducing leukemia stem cell differentiation

Research Project

Project/Area Number	15H06037
Research Category	Grant-in-Aid for Research Activity Start-up
Allocation Type	Single-year Grants
Research Field	General medical chemistry
Research Institution	Tohoku University
Principal Investigator	YU Lei 東北大学, 医学系研究科, 産学官連携研究員 (00760654)
Project Period (FY)	2015-08-28 – 2017-03-31
Project Status	Completed (Fiscal Year 2016)
Budget Amount *help	¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000) Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	Gata1 gene regulation / Erythropoiesis / Apoptosis / leukamia stem cell / GATA1 / apoptosis / Hematopoietic stem cell / Leukemia stem cell
Outline of Final Research Achievements	I identified the crucial mechanism of erythropoiesis initiation from hematopoietic stem and progenitor cells (HSPCs). By generating several lines of Gata1 bacterial artificial chromosome transgenic mice in which the HSPC specific silencer was deleted, I could be able to induce high level of Gata1 or CreERT2 expression in HSPCs. By using these mouse models as well as Dnmt1 conditional knockout allele, I found the demethylation of enhancers (which was methylated and repressed by the HSPC specific silencer) of erythroid master transcription factor GATA1, and therefore the gene activation, is the key of the initiation of red blood cell differentiation.