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研究领域生物医学和临床科学瘤学和致癌症预测和预后标志物
阿斯巴拉金合成酶标志着心肌细胞分化的明显依赖值

阿斯巴拉金合成酶标志着心肌细胞分化的明显依赖值

Yike Zhu ^1,2, Matthew Ackers-Johnson ^1,2, Muthu K Shanmugam ^1,2, Leroy Sivappiragasam Pakkiri ^1,3, Chester Lee Drum ^1,3, Yanpu Chen , Johnny Kim ^3,4, Wyatt G Paltzer ⁵, Ahmed I Mahmoud ⁵, Wilson Lek Wen Tan ^1,2, Mick Chang Jie Lee ^1,2, Jianming Jiang ^1,2, Danh Anh Tuan Luu ^1,2, Shi Ling Ng ^1,2, Peter Yi Qing Li ^1,2, Anhui Wang ^6,7, Rong Qi ^6,7, Gabriel Jing Xiang Ong ^1,2, Timothy Yu Ng ^1,2, Jody J Haigh ^8,9, Zenia Tiang ^1,2, A Mark Richards ^1,2,10, Roger S Y Foo ^1,2,11

Yike Zhu ^1,2, Matthew Ackers-Johnson ^1,2, Muthu K Shanmugam ^1,2

¹Cardiovascular Research Institute, Yong Loo Lin School of Medicine, National University of Singapore (Y.Z., M.A.-J., M.K.S., L.S.P., C.L.D., W.L.W.T., M.C.J.L., J.J., L.D.A.T., S.L.N., P.Y.Q.L. G.J.X.O., T.Y.N., Z.T., A.M.R., R.S.Y.F.).
²Cardiovascular Metabolic Disease Translational Research Programme (Y.Z., M.A.-J., M.K.S., L.S.P., C.L.D., W.L.W.T., M.C.J.L., J.J., L.D.A.T., S.L.N., P.Y.Q.L. G.J.X.O., T.Y.N., Z.T., A.M.R., R.S.Y.F.), National University Health Systems, Singapore.
³Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (C.Y., J.K.).
⁴German Centre for Cardiovascular Research (DZHK), Partner site Rhein/Main, Bad Nauheim (J.K.).
⁵Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin-Madison (W.G.P., A.I.M.).
⁶Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Centre (W.A., Q.R.), Peking University, China.
⁷State Key Laboratory of Vascular Homeostasis and Remodelling (W.A., Q.R.), Peking University, China.
⁸CancerCare Manitoba Research Institute, Department of Pharmacology and Therapeutics, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada (J.J.H.).
⁹VIB, Flanders Institute for Biotechnology, Ghent University, Ghent, Belgium (J.J.H.).
¹⁰Christchurch Heart Institute, University of Otago, New Zealand (A.M.R.).
¹¹Institute of Molecular and Cell Biology, A*STAR, Singapore (R.S.Y.F.).

⁰Cardiovascular Research Institute, Yong Loo Lin School of Medicine, National University of Singapore (Y.Z., M.A.-J., M.K.S., L.S.P., C.L.D., W.L.W.T., M.C.J.L., J.J., L.D.A.T., S.L.N., P.Y.Q.L. G.J.X.O., T.Y.N., Z.T., A.M.R., R.S.Y.F.).

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2024年四月8日

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在PubMed上查看摘要

概括

此摘要是机器生成的。

研究人员确定阿斯巴拉金合成酶 (Asns) 是心肌细胞分化 (CMDD) 的关键标志物和媒介,对心脏再生至关重要. 在成年心肌细胞中,Asns和mTORC1通路对于这一过程至关重要.

科学领域

心血管生物学
细胞和分子医学
复原医学

背景情况

成年哺乳动物心肌细胞由于增殖受限而具有有限的再生能力.
心肌细胞脱差 (CMDD) 在细胞循环重新进入和心脏再生之前,代表了一个独特的过渡细胞状态.
了解CMDD对于制定改善心脏修复的策略至关重要.

研究的目的

确定心肌细胞分离的常见分子标志物 (CMDD).
研究已识别的标记物在心肌细胞循环再进入和心脏再生中的作用.

主要方法

使用体外培养的成年小鼠心肌细胞和体内AAV9介导的重编程因子 (Oct4,Sox2,Klf4,Myc).
使用现有数据集进行RNA测序和综合分析,以确定CMDD的共同分子分母.
在各种实验模型中研究了已识别的标记基因的功能.

主要成果

确定了阿斯巴拉金合成酶 (Asns) 作为一种与CMDD强烈相关的独特分子标志物.
证明阿斯纳斯对阿斯巴拉金的增加和氨基酸流量的改变是必要的.
在新生儿心肌梗塞模型中,Asns缺乏会损害再生,并通过mTORC1途径影响成年心肌细胞循环.

结论

发现Asns作为CMDD的新型标志物和基本介质,在多种模型中很常见.
揭示了Asns/mTORC1轴对心肌细胞的分化依赖.
突出了Asns作为心脏再生的治疗目标的潜力.

关键词:

细胞脱差细胞自我更新肌细胞,心脏进行再生

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