Reduction of Intracellular Tension and Cell Adhesion Promotes Open Chromatin Structure and Enhances Cell Reprogramming.
Reduction of Intracellular Tension and Cell Adhesion Promotes Open Chromatin Structure and Enhances Cell Reprogramming.
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DOI：
10.1002/advs.202300152
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发表时间：
2023-08
期刊：
影响因子：
15.1
通讯作者：
Li, Song
中科院分区：
文献类型：
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作者：
Soto, Jennifer;Song, Yang;Wu, Yifan;Chen, Binru;Park, Hyungju;Akhtar, Navied;Wang, Peng-Yuan;Hoffman, Tyler;Ly, Chau;Sia, Junren;Wong, SzeYue;Kelkhoff, Douglas O.;Chu, Julia;Poo, Mu-Ming;Downing, Timothy L.;Rowat, Amy C.;Li, Song
转录因子和生物分子在细胞类型转换中的作用已被广泛研究。然而，目前尚不清楚是否以及如何通过粘着斑（FA）和细胞骨架的细胞内机械转导调节表观遗传状态和细胞重编程。在这里，它表明，细胞骨架结构和机械性能的细胞在诱导的神经元（iN）重编程的早期阶段调制，增加肌动蛋白细胞骨架组装Ascl1转基因诱导。在重编程的早期阶段，肌动蛋白细胞骨架张力或细胞粘附的降低抑制了间充质基因的表达，促进了更开放的染色质结构，并显著提高了iN转化的效率。具体而言，细胞内张力或细胞粘附的降低不仅调节全局表观遗传标记，而且减少DNA甲基化和异染色质标记，并增加神经元基因启动子处的常染色质标记，从而增强基因激活的可及性。最后，减少细胞粘附的微米和纳米形貌表面增强了iN重编程。这些新的发现表明，肌动蛋白细胞骨架和脂肪酸在细胞命运决定的表观遗传调控中起着重要作用，这可能会导致新的工程方法用于细胞重编程。在这里，它表明，细胞骨架结构和机械性能的细胞在诱导神经元（iN）重编程的早期阶段调制。在重编程的早期阶段，肌动蛋白细胞骨架张力或细胞粘附的降低抑制了间充质基因的表达，促进了更开放的染色质结构，并显著提高了iN转化的效率。
The role of transcription factors and biomolecules in cell type conversion has been widely studied. Yet, it remains unclear whether and how intracellular mechanotransduction through focal adhesions (FAs) and the cytoskeleton regulates the epigenetic state and cell reprogramming. Here, it is shown that cytoskeletal structures and the mechanical properties of cells are modulated during the early phase of induced neuronal (iN) reprogramming, with an increase in actin cytoskeleton assembly induced by Ascl1 transgene. The reduction of actin cytoskeletal tension or cell adhesion at the early phase of reprogramming suppresses the expression of mesenchymal genes, promotes a more open chromatin structure, and significantly enhances the efficiency of iN conversion. Specifically, reduction of intracellular tension or cell adhesion not only modulates global epigenetic marks, but also decreases DNA methylation and heterochromatin marks and increases euchromatin marks at the promoter of neuronal genes, thus enhancing the accessibility for gene activation. Finally, micro‐ and nano‐topographic surfaces that reduce cell adhesions enhance iN reprogramming. These novel findings suggest that the actin cytoskeleton and FAs play an important role in epigenetic regulation for cell fate determination, which may lead to novel engineering approaches for cell reprogramming. Here, it is shown that cytoskeletal structures and the mechanical properties of cells are modulated during the early phase of induced neuronal (iN) reprogramming. The reduction of actin cytoskeletal tension or cell adhesion at the early phase of reprogramming suppresses the expression of mesenchymal genes, promotes a more open chromatin structure, and significantly enhances the efficiency of iN conversion.
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影响因子：
64.8
作者：
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通讯作者：
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