在斑马鱼体内,mTORC1 通过核糖体生物生成蛋白 Urb2 介导造血干细胞和祖细胞的扩增。

IF 5.9 2区 医学 Q1 CELL & TISSUE ENGINEERING
Stem Cell Reports Pub Date : 2024-09-10 Epub Date: 2024-08-22 DOI:10.1016/j.stemcr.2024.07.011
Wenming Huang, Yu Yue, Weifeng Hao, Zhenan Zhang, Pengcheng Cai, Deqin Yang
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引用次数: 0

摘要

哺乳动物雷帕霉素靶标(mTOR)是控制蛋白质合成、细胞生长和存活的关键传感器。尽管有报道称 mTOR 可调控小鼠造血干细胞和祖细胞(HSPC)的移植和多系造血,但独特的 mTOR 复合物(mTORC)在早期 HSPC 发育和 HSPC 池形成中的作用尚未得到充分阐明。在这里,我们发现 mTORC1 对斑马鱼早期 HSPC 的扩增至关重要。mTORC1 信号在确定性 HSPC 的萌发和扩增阶段被高度激活。药理学或遗传学上的 mTORC1 失活会导致细胞增殖紊乱,从而导致 HSPC 扩增和迁移缺陷。有趣的是,mTORC2 对于早期 HSPC 的发育是不可或缺的。核糖体生物发生蛋白Urb2在mTORC1抑制时下调,而urb2的过表达部分挽救了mTORC1缺陷胚胎的造血缺陷。这些数据表明,mTORC1 信号通过 Urb2 调节早期 HSPC 的扩增,这项工作将加深我们对不同生理过程中 mTOR 的理解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
mTORC1 mediates the expansion of hematopoietic stem and progenitor cells through ribosome biogenesis protein Urb2 in zebrafish.

Mammalian target of rapamycin (mTOR) serves as the key sensor to control protein synthesis, cell growth, and survival. Despite mTOR is reported to regulate hematopoietic stem and progenitor cell (HSPC) engraftment and multiple-lineage hematopoiesis in mice, the roles of unique mTOR complexes (mTORCs) in early HSPC development and HSPC pool formation have not been adequately elucidated. Here, we uncover that mTORC1 is essential for early HSPC expansion in zebrafish. mTORC1 signaling was highly activated in definitive HSPCs during the emerging and expanding stages. Pharmacological or genetic inactivation of mTORC1 would cause defective HSPC expansion and migration due to disrupted cell proliferation. Interestingly, mTORC2 is dispensable for early HSPC development. Ribosome biogenesis protein Urb2 was downregulated upon mTORC1 inhibition, and urb2 overexpression partially rescued the hematopoietic defects in mTORC1-deficient embryos. These data demonstrate that mTORC1 signaling regulates early HSPC expansion through Urb2, and this work will deepen our understanding of mTOR in different physiological processes.

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来源期刊
Stem Cell Reports
Stem Cell Reports CELL & TISSUE ENGINEERING-CELL BIOLOGY
CiteScore
10.50
自引率
1.70%
发文量
200
审稿时长
28 weeks
期刊介绍: Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.
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