Analysis of organelle functions for the homeostasis of hematopoietic stem cells and platelet production

造血干细胞稳态和血小板生成的细胞器功能分析

• 批准号: 22H03107
• 负责人: 石津 綾子
• 金额: $ 11.23万
• 依托单位: Tokyo Women's Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2022
• 资助国家: 日本
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-22H03107/
• 关键词: 造血幹細胞; ミトコンドリア; 血小板分化; 巨核球; ライソソーム; オルガネラ; 血小板; とトンボポエチン

一生涯にわたる恒常的な血球産生には造血幹細胞(hematopoietic stem cell: HSC)の維持・増殖・分化が不可欠である。サイトカインであるThrombopoietin(Thpo)はHSCを直接刺激し血小板産生とHSC維持を促す。Thpoシグナルは成人期HSCの自己複製能と細胞周期静止期保持に必須のシグナルであり、mitochondriaをはじめHSCの代謝調整に深く関連する。HSCは低酸素状態の骨髄微細環境内で、エネルギー代謝活性の低いmitochondriaを多く保有する。しかし、活性の低いmitochondriaの存在意義、HSC維持や分化に与える影響、及び他の細胞内小器官(オルガネラ)との関連性は解明されていない。本研究は、Thpoシグナルによるオルガネラ代謝変動がHSCの維持と血小板分化運命に与える影響を解明することを目的とした。具体的な計画とし(1) Thpoシグナルによるmitochondria鉄動態とHSC維持・分化機構、(2) 単一HSC解析によるThpo応答性とオルガネラ状態で規定されるheterogeneity、(3) Thpoを介したオルガネラ調整によるHSC血小板系統分化機構を行っている。本年度は(1) Thpoシグナルによるmitochondria鉄動態とHSC維持・分化機構を解析し、Thpoシグナル欠損では造血幹細胞のMitochondria鉄が増幅し、造血幹細胞機能及びオルガネラ恒常性に障害を与えることを解析した。現在、論文投稿中である。

The constant hematopoietic progenitor cells (hematopoietic stem cell: HSC) in the whole life can maintain the differentiation of colonies. Direct stimulation of platelet production and HSC maintenance by Thrombopoietin (Thpo) HSC. In adulthood, HSC copies itself in adulthood. During the quiescent phase of the cell cycle, it is necessary to keep the cell cycle at rest. It is necessary to reorganize the cell cycle during the rest of the cell cycle, and the HSC gene must be reorganized on behalf of the Thpo gene. HSC has a low acid state, and its activity is low, mitochondria is low, and its activity is high. The meaning of the existence of active and low-level mitochondria, the relationship between differentiation and differentiation, and the connectivity of small intracellular organs (small organs) in other cells. In this study, Thpo and HSC were used to maintain the life cycle of platelet differentiation and to understand the purpose of platelet differentiation. Specific plans: (1) Thpo response (HSC) differentiation mechanism (HSC), (2) HSC analysis of Thpo response response status regulation (heterogeneity), (3) Thpo regulation regulation, and (3) regulatory regulation of platelet differentiation mechanism. This year, (1) Thpo is responsible for the maintenance of mitochondria dynamics, HSC maintenance and differentiation, Thpo is not responsible for hematopoietic cell cycle Mitochondria, hematopoietic cell function and hematopoietic cell function, and the constant disorder is analyzed and analyzed. At present, I am in the process of submitting articles.

项目成果

Fanconi anemia-related replication stress activates metabolism in fetal liver hematopoietic stem cells

范可尼贫血相关的复制应激激活胎儿肝脏造血干细胞的代谢

• 发表时间: 2022
• 作者: Shiroshita Kohei;Kobayashi Hiroshi;Watanuki Shintaro;Karigane Daiki;Sorimachi Yuriko;Fujita Shinya;Tamaki Shinpei;Haraguchi Miho;Itokawa Naoki;Aoyama Kazumasa;Koide Shuhei;Masamoto Yosuke;Kobayashi Kenta;Nakamura-Ishizu Ayako;Kurokawa Mineo;Iwama Atsushi;Ayako Nakamura-Ishizu;Ayako Nakamura-Ishizu;望月牧子;Ayako Nakamura-Ishizu;望月牧子
• 通讯作者: 望月牧子

Replication stress increases mitochondrial metabolism and mitophagy in FANCD2 deficient fetal liver hematopoietic stem cells.

• DOI: 10.3389/fonc.2023.1108430
• 发表时间: 2023
• 期刊: Frontiers in oncology
• 影响因子: 4.7

Ptprd regulates hematopoietic stem cells through their microelement domains

Ptprd 通过微量元素域调节造血干细胞

• 发表时间: 2022
• 作者: Shiroshita Kohei;Kobayashi Hiroshi;Watanuki Shintaro;Karigane Daiki;Sorimachi Yuriko;Fujita Shinya;Tamaki Shinpei;Haraguchi Miho;Itokawa Naoki;Aoyama Kazumasa;Koide Shuhei;Masamoto Yosuke;Kobayashi Kenta;Nakamura-Ishizu Ayako;Kurokawa Mineo;Iwama Atsushi;Ayako Nakamura-Ishizu;Ayako Nakamura-Ishizu;望月牧子
• 通讯作者: 望月牧子

Thrombopoietin-mediated regulation of mitochondria metabolism in hematopoietic stem cells

血小板生成素介导的造血干细胞线粒体代谢调节

• 发表时间: 2022
• 作者: Shiroshita Kohei;Kobayashi Hiroshi;Watanuki Shintaro;Karigane Daiki;Sorimachi Yuriko;Fujita Shinya;Tamaki Shinpei;Haraguchi Miho;Itokawa Naoki;Aoyama Kazumasa;Koide Shuhei;Masamoto Yosuke;Kobayashi Kenta;Nakamura-Ishizu Ayako;Kurokawa Mineo;Iwama Atsushi;Ayako Nakamura-Ishizu;Ayako Nakamura-Ishizu;望月牧子;Ayako Nakamura-Ishizu
• 通讯作者: Ayako Nakamura-Ishizu