|Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
|Outline of Final Research Achievements
To clarify a role of OLFM4, a gene located in the commonly deleted region of 13q, in the preferential commitment of hematopoietic stem cells (HSCs) with del(13q) in patients with autoimmune hematopoietic failure, we examined the effects of OLFM4 knockout or knockdown in a leukemia cell line TF-1 and CD34+ cells derived from iPS cells or from cord blood. The OLFM4 gene downregulation promoted erythroid differentiation of both TF-1 and CD34+ cells induced by TGF-β. Similarly augmented erythroid differentiation was observed in HSCs that underwent the knockout of a GPI-anchored protein CD109. Haploinsufficiency of OLFM4 as a result of del(13q) may thus explain the preferential commitment of HSCs with del(13q) in bone marrow failure patients with paroxysmal nocturnal hemoglobinuria-phenotype cells.