| Project/Area Number |
18K14713
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 44020:Developmental biology-related
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| Research Institution | Kyoto University |
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Principal Investigator |
Kidani Yohko 京都大学, iPS細胞研究所, 特別研究員(PD) (20811409)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 血球分化 / エンハンサー制御 / 造血幹細胞 / エピジェネティックス / エンハンサー / 細胞分化 |
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| Outline of Final Research Achievements |
In this study, we aimed to elucidate the transcriptional and epigenetic regulation governing human hematopoietic progenitor cell differentiation. With cord blood-derived hematopoietic stem cells as a reference, we utilized embryonic stem cell- or induced pluripotent stem cell-derived hematopoietic cell differentiation system in vitro in order to capture spatiotemporal regulation of cell differentiation from the beginning. By comprehensively analyzing molecular changes during hematopoietic cell differentiation, we picked up candidate regulators in silico and tested their functionality by genome editing. As a result, we found a novel regulator which was essential for hematopoietic cell differentiation. It appeared to control arterialization of endothelial cells, which recently was found to be a prerequisite for hematopoiesis. Thus, our results provide a novel insight of hematopoietic cell differentiation.
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| Academic Significance and Societal Importance of the Research Achievements |
ヒト造血幹細胞は様々な免疫細胞に分化する能力を持つため、造血不全や血液腫瘍などの疾患において重要な移植ターゲットである。しかし、慢性的なドナー不足が問題であり、ヒト人工多能性幹(iPS)細胞を用いて人工的に造血幹細胞を作製する手法確立が求められている。近年遺伝子発現解析を中心に、造血幹細胞分化に関わる転写因子が同定されてきているが、未だ分化制御の全貌は明らかでない。本研究では、特にエンハンサー制御に注目することで、血球分化に必要な新規制御因子を同定した。この因子およびその下流分子を操作することで、効率よく血球分化を誘導する手法確立が期待される。
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