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2020 Fiscal Year Final Research Report

The maintenance of hematopoietic stem cells through tuning TPO response

Research Project

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Project/Area Number 19K22641
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
Research InstitutionKumamoto University

Principal Investigator

Umemoto Terumasa  熊本大学, 国際先端医学研究機構, 特任准教授 (50620225)

Project Period (FY) 2019-06-28 – 2021-03-31
Keywords造血幹細胞
Outline of Final Research Achievements

In this study, we found that the regulation of glucose or glutamine uptake is important to regulate the differentiation of hematopoietic stem cells (HSCs in the presence of Thrombopoietin (TPO), which have multi-functions in HSCs. In addition, we suggested that HSCs regulate TPO responses through changing chromatin accessibility pattern. In addition of the change of changing chromatin accessibility pattern, Acly-dependent histone acetylation is required to induce the differentiation of HSCs under TPO stimulation. Moreover, the combination between low nutrition and Acly suppression contributes to the maintenance of stem-ness especially within the rapidly divided HSC fraction.

Free Research Field

幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究の結果は、造血幹細胞における「Thrombopoietin (TPO)」の相反する効果が制御されるメカニズムの一端を明らかにした。さらに、幹細胞研究において、「自己複製・分化誘導の選択機構」の解明は古くからの大きな問いであり、本研究の成果は、TPO刺激をモデルとして、その機構の解明に寄与したと考えられる。さらに、TPO刺激と代謝制御が試験管内での造血幹細胞維持に寄与することも見出した。従って、本研究の成果は「造血幹細胞の増幅・維持が可能な培養条件」の開発に寄与すると考えられ、将来的には、骨髄移植療法の質・安全・適応の拡大や、造血幹細胞を用いた遺伝子療法にも大きく貢献すると考えられる。

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Published: 2022-01-27  

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