Mechanomics analysis of hESCs under combined mechanical shear, stretch, and compression

Mechanomics analysis of hESCs under combined mechanical shear, stretch, and compression
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hESC 在机械剪切、拉伸和压缩联合作用下的力学分析

DOI:
10.1007/s10237-020-01378-5
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发表时间:
2020-08
影响因子:
3.5
通讯作者:
Long M.
Long M.
中科院分区:
工程技术2区
文献类型:
--
作者:
Zhang F.;Wang J.W.;Lü D.Y.;Zheng L.;Shangguan B.;Gao Y.X.;Wu Y.;Long M.

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人类胚胎干细胞(hESC)可以在生物化学和生物力学小生境中分化为三个胚层。体内复杂的力学环境对hESCs的命运决定和生物学功能具有不同的影响。为了全面筛选机械敏感分子,需要三种典型的机械刺激类型,即,拉伸拉伸、剪切流动和机械压缩,应用于载荷模式、振幅、频率和/或持续时间的相应参数组,然后,iTRAQ蛋白质组学测试用于鉴定和定量hESC中差异表达的蛋白质。生物信息学分析确定了37,41,和23蛋白拉伸模式下,频率和持续时间,13,18,和41蛋白剪切模式下,振幅和持续时间,和4,0,和183蛋白压缩振幅,频率和持续时间,分别在不同的参数下产生的差异加权的偏好,在每个刺激。10个机械敏感的蛋白质之间共享的两个三个机械刺激,以及许多蛋白质在单一刺激下确定。更重要的是,功能GSEA和WGCNA分析阐述了筛选的蛋白质随加载参数的变化。蛋白质合成和修饰的共同功能被确定在三种刺激中,并且在单独拉伸下的皮肤发育中观察到特定功能。总之,机械组学分析是必不可少的映射实际机械敏感蛋白在生理模拟机械环境下,并揭示了理解的核心枢纽蛋白在机械生物学。
Human embryonic stem cells (hESCs) can differentiate to three germ layers within biochemical and biomechanical niches. The complicated mechanical environments in vivo could have diverse effects on the fate decision and biological functions of hESCs. To globally screen mechanosensitive molecules, three typical types of mechanical stimuli,i.e.,tensile stretch, shear flow, and mechanical compression, were applied in respective parameter sets of loading pattern, amplitude, frequency, and/or duration, and then, iTRAQ proteomics test was used for identifying and quantifying differentially expressed proteins in hESCs. Bioinformatics analysis identified 37, 41, and 23 proteins under stretch pattern, frequency, and duration, 13, 18, and 41 proteins under shear pattern, amplitude, and duration, and 4, 0, and 183 proteins under compression amplitude, frequency, and duration, respectively, where distinct parameters yielded the differentially weighted preferences under each stimulus. Ten mechanosensitive proteins were commonly shared between two of three mechanical stimuli, together with numerous proteins identified under single stimulus. More importantly, functional GSEA and WGCNA analyses elaborated the variations of the screened proteins with loading parameters. Common functions in protein synthesis and modification were identified among three stimuli, and specific functions were observed in skin development under stretch alone. In conclusion, mechanomics analysis is indispensable to map actual mechanosensitive proteins under physiologically mimicking mechanical environment, and sheds light on understanding the core hub proteins in mechanobiology.
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