Analysis of the regulation of early erythropoiesis by transcription factor GATA1 and erythropoietin signal

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17392
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Tohoku University
• Principal Investigator: Hirano Ikuo 東北大学, 医学系研究科, 講師 (00708117)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: GATA1 / Erythropoiesis / differentiation / EPO

Outline of Final Research Achievements

The purpose of this study was to elucidate the details of the regulatory mechanism of erythropoiesis by EPO, a cytokine that promotes erythropoiesis, and GATA1, a transcription factor that regulates erythroid differentiation. I performed a comparative analysis using mice in which GATA1 KD or GATA1 KO cells could be compared to normal cells within the same individual. The results showed that GATA1 is essential for differentiation at the MEP stage and that GATA1 KD cells produce an abnormal cell cluster that exhibits a specific gene expression pattern. We also suggested that GATA1 regulates EPO signaling by regulating Epor gene expression during the MEP stage, while there is no regulation of Gata1 gene expression by EPO signaling.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

赤血球は、その分化過程において造血幹細胞から段階的に分化が進み運命決定される。GATA1転写因子は赤血球分化のマスター転写因子として知られており、赤血球分化過程の広範な段階を制御しているが、比較的その発現量の少ない分化段階初期における機能については、その標的遺伝子を含め不明であった。本研究は、GATA1が機能する最初期の赤血球分化過程における働きを明らかとするものであり、将来的にiPS細胞等からの効率的な赤血球分化誘導系の最適化や、種々の貧血を伴う血液疾患の治療法の開発につながると考えている。