Biphasic regulation of epigenetic state by matrix stiffness during cell reprogrammingopen access
- Authors
- Song, Yang; Soto, Jennifer; Wong, Sze Yue; Wu, Yifan; Hoffman, Tyler; Akhtar, Navied; Norris, Sam; Chu, Julia; Park, Hyungju; Kelkhoff, Douglas O.; Ang, Cheen Euong; Wernig, Marius; Kasko, Andrea; Downing, Timothy L.; Poo, Mu-ming; Li, Song
- Issue Date
- Feb-2024
- Publisher
- AMER ASSOC ADVANCEMENT SCIENCE
- Citation
- SCIENCE ADVANCES, v.10, no.7
- Journal Title
- SCIENCE ADVANCES
- Volume
- 10
- Number
- 7
- URI
- http://scholarworks.bwise.kr/kbri/handle/2023.sw.kbri/1162
- DOI
- 10.1126/sciadv.adk0639
- ISSN
- 2375-2548
2375-2548
- Abstract
- We investigate how matrix stiffness regulates chromatin reorganization and cell reprogramming and find that matrix stiffness acts as a biphasic regulator of epigenetic state and fibroblast-to-neuron conversion efficiency, maximized at an intermediate stiffness of 20 kPa. ATAC sequencing analysis shows the same trend of chromatin accessibility to neuronal genes at these stiffness levels. Concurrently, we observe peak levels of histone acetylation and histone acetyltransferase (HAT) activity in the nucleus on 20 kPa matrices, and inhibiting HAT activity abolishes matrix stiffness effects. G-actin and cofilin, the cotransporters shuttling HAT into the nucleus, rises with decreasing matrix stiffness; however, reduced importin-9 on soft matrices limits nuclear transport. These two factors result in a biphasic regulation of HAT transport into nucleus, which is directly demonstrated on matrices with dynamically tunable stiffness. Our findings unravel a mechanism of the mechano-epigenetic regulation that is valuable for cell engineering in disease modeling and regenerative medicine applications.
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Collections - 연구본부 > 신경·혈관 단위체 연구그룹 > 1. Journal Articles
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