Nicher Regulation for Normal Hemopoietic Stem Cells and Leukemic Stem Cells

正常造血干细胞和白血病干细胞的利基调节

• 批准号: 23249053
• 负责人: SUDA Toshio
• 金额: $ 30.78万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-23249053/
• 关键词: 造血幹細胞; 白血病幹細胞; ニッチ; 活性酸素; 低酸素; 炎症; プロスタグランディン; ニッチ因子

Stem cell maintenance in a haltered cell-cycle state (i.e., quiescence) has been proposed as a fundamental property of HSCs. Maintenance of quiescence protects HSCs from functional exhaustion and naturally producing extrinsic cellular insults to enable lifelong hematopoietic cell production. HSC quiescence is regulated through a complex network of cell intrinsic regulations along with extrinsic influences from the microenvironment. Normal HSCs maintain intracellular hypoxia, stabilize the hypoxia-inducible factor-alpha(HIF-1a) protein and generate ATP by anaerobic metabolism. In HIF-1a-deficiency, HSCs became metabolically aerobic, lost cell cycle quiescence, and finally exhausted.

干细胞维持在停滞的细胞周期状态（即，静止）被认为是HSC的基本特性。静止的维持保护HSC免于功能衰竭和天然产生的外源性细胞损伤，以实现终身造血细胞产生。HSC静止是通过细胞内在调控沿着来自微环境的外在影响的复杂网络来调节的。正常HSC维持细胞内缺氧，稳定缺氧诱导因子-α（HIF-1a）蛋白并通过无氧代谢产生ATP。在HIF-1a缺乏时，HSC变得代谢需氧，失去细胞周期静止期，并最终耗尽。

项目成果

Hematopoietic stem cells in hypoxic niches

缺氧环境中的造血干细胞

• 发表时间: 2012
• 作者: 堀江公仁子;兒玉啓輔;高山賢一;池田和博;井上聡;北村俊雄;Suda T
• 通讯作者: Suda T

Glycolytic metabolism of hematopoieic stem cells

造血干细胞的糖酵解代谢

• 发表时间: 2011
• 作者: Tomoko T;Koji Y;Yoji K;Koichiro H;Kiyoko K;Norio W;Kenshi H;Suda T
• 通讯作者: Suda T

Glycolytic metabolism of hematopoietic stem cells

造血干细胞的糖酵解代谢

• 发表时间: 2011
• 作者: Gao J;Inagaki Y;Song P;Qu X;Kokudo N;Tang W;Suda T
• 通讯作者: Suda T

Normal haematopoietic stem cells and the stem cell niche

正常造血干细胞和干细胞生态位

• 发表时间: 2011
• 作者: Uchida K;Yasunaga H;Sumitani M;Horiguchi H;Fushimi K;Yamada Y;Suda T
• 通讯作者: Suda T

Metabolic requirements for the maintenance of self-renewing stem cells.

• DOI: 10.1038/nrm3772
• 发表时间: 2014-04
• 期刊: Nature reviews. Molecular cell biology