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TMT-based quantitative proteome profiles reveal the memory function of a whole heart decellularized matrix for neural stem cell trans-differentiation into the cardiac lineage

机译:基于TMT的定量蛋白质组曲线揭示了整个心脏脱细胞的记忆功能,用于神经干细胞转化为心脏谱系

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摘要

Whole organ or tissue decellularized matrices are a promising scaffold for tissue engineering because they maintain the specific memory of the original organ or tissue. A whole organ or tissue decellularized matrix contains extracellular matrix (ECM) components, and exhibits ultrastructural and mechanical properties, which could significantly regulate the fate of stem cells. To better understand the memory function of whole organ decellularized matrices, we constructed a heart decellularized matrix and seeded cross-embryonic layer stem cells - neural stem cells (NSCs) to repopulate the matrix, engineering cardiac tissue, in which a large number of NSCs differentiated into the neural lineage, but besides that, NSCs showed an obvious tendency of trans-differentiating into cardiac lineage cells. The results demonstrated that the whole heart decellularized microenvironment possesses memory function. To reveal the underlying mechanism, TMT-based quantitative proteomics analysis was used to identify the differently expressed proteins in the whole heart decellularized matrix compared with a brain decellularized matrix. 937 of the proteins changed over 1.5 fold, with 573 of the proteins downregulated and 374 of the proteins upregulated, among which integrin ligands in the ECM serve as key signals in regulating NSC fate. The findings here provide a novel insight into the memory function of tissue-specific microenvironments and pave the way for the therapeutic application of personalized tissues.
机译:整个器官或组织脱细胞的基质是用于组织工程的有前途的支架,因为它们保持了原始器官或组织的特定记忆。整个器官或组织脱细胞化基质含有细胞外基质(ECM)组分,并且表现出超微结构和机械性能,这可以显着调节干细胞的命运。为了更好地理解整个器官脱细胞的矩阵的记忆功能,我们构建了一种心脏脱细胞的基质和种子横胚层干细胞 - 神经干细胞(NSCs),以汇编基质,工程心脏组织,其中大量的NSCs差异化进入神经谱系,但除此之外,NSCs显示出反向心脏谱系细胞的明显趋势。结果表明,整个心脏脱细胞化微环境具有记忆功能。为了揭示潜在的机理,基于TMT的定量蛋白质组学分析用于鉴定与脑脱细胞的基质相比全心脏脱细胞基质中不同表达的蛋白质。 937蛋白质的变化超过1.5倍,其中573个蛋白质下调,374个蛋白质上调,ECM中的整联蛋白配体作为调节NSC命运的关键信号。这里的发现提供了一种对组织特异性微环境的记忆功能的新颖洞察力,并为个性化组织的治疗应用铺平了道路。

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  • 来源
    《Biomaterials Science》 |2021年第10期|共13页
  • 作者单位

    Beijing Inst Basic Med Sci 27 Taiping Rd Beijing 100850 Peoples R China;

    Beijing Inst Basic Med Sci 27 Taiping Rd Beijing 100850 Peoples R China;

    Beijing Inst Basic Med Sci 27 Taiping Rd Beijing 100850 Peoples R China;

    Beijing Inst Basic Med Sci 27 Taiping Rd Beijing 100850 Peoples R China;

    Beijing Inst Basic Med Sci 27 Taiping Rd Beijing 100850 Peoples R China;

    Beijing Inst Basic Med Sci 27 Taiping Rd Beijing 100850 Peoples R China;

    Beijing Inst Basic Med Sci 27 Taiping Rd Beijing 100850 Peoples R China;

    Beijing Inst Basic Med Sci 27 Taiping Rd Beijing 100850 Peoples R China;

    Beijing Inst Basic Med Sci 27 Taiping Rd Beijing 100850 Peoples R China;

    Beijing Inst Basic Med Sci 27 Taiping Rd Beijing 100850 Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分子生物学;
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