Reduction of Intracellular Tension and Cell Adhesion Promotes Open Chromatin Structure and Enhances Cell Reprogramming

Autor: Jennifer Soto, Yang Song, Yifan Wu, Binru Chen, Hyungju Park, Navied Akhtar, Peng‐Yuan Wang, Tyler Hoffman, Chau Ly, Junren Sia, SzeYue Wong, Douglas O. Kelkhoff, Julia Chu, Mu‐Ming Poo, Timothy L. Downing, Amy C. Rowat, Song Li
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Advanced Science, Vol 10, Iss 24, Pp n/a-n/a (2023)
Druh dokumentu: article
ISSN: 2198-3844
68534698
DOI: 10.1002/advs.202300152
Popis: Abstract 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.
Databáze: Directory of Open Access Journals
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