Mitochondrial transfer RNA modifications in normal and stressed hematopoiesis

正常和应激造血过程中线粒体转移 RNA 修饰

• 批准号: 18K16124
• 负责人: FAKRUDDIN MD
• 金额: $ 2.16万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Early-Career Scientists
• 财政年份: 2018
• 资助国家: 日本
• 起止时间: 2018-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-18K16124/
• 关键词: mitochondria; tRNA modification; Hematopoiesis; Mitochondria; tRNA; Modification

We generated hematopoiesis specific MTO1 knock out mice (vav-iCre: MTO1 KO) and found that the KO mice was embryonic lethal due to severe anemia. Hematopoietic stem cell population was changed significantly in the embryos. Erythrocyte progenitors analysis did not showed any defect in the progenitor level. To study the mechanisms further, we also generated tamoxifen inducible HSC specific conditional MTO1 knock out mice (Hlf-Cre ERT2: MTO1 cKO) and will analyze these mice very soon. Furthermore, to study the role of MTO1 in HSC niche, i am generating niche specific MTO1 knock out mice (LepR cre: MTO1 KO). Comprehensive analysis of these mouse models at cellular and molecular level will delineate the novel role transfer RNA modifications in normal and stressed hematopoiesis.

我们培育了造血特异性 MTO1 敲除小鼠（vav-iCre：MTO1 KO），发现 KO 小鼠因严重贫血而胚胎致死。胚胎中的造血干细胞群发生了显着变化。红细胞祖细胞分析未显示祖细胞水平有任何缺陷。为了进一步研究其机制，我们还生成了他莫昔芬诱导的 HSC 特异性条件性 MTO1 敲除小鼠 (Hlf-Cre ERT2: MTO1 cKO)，并将很快对这些小鼠进行分析。此外，为了研究 MTO1 在 HSC 生态位中的作用，我正在生成生态位特异性 MTO1 敲除小鼠（LepR cre：MTO1 KO）。在细胞和分子水平上对这些小鼠模型进行综合分析将描述转移 RNA 修饰在正常和应激造血过程中的新作用。