Transient nuclear deformation primes epigenetic state and promotes cell reprogramming

Yang Song, Jennifer Soto, Binru Chen, Tyler Hoffman, Weikang Zhao, Ninghao Zhu, Qin Peng, Longwei Liu, Chau Ly, Pak Kin Wong, Yingxiao Wang, Amy C. Rowat, Siavash K. Kurdistani, Song Li

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Cell reprogramming has wide applications in tissue regeneration, disease modelling and personalized medicine. In addition to biochemical cues, mechanical forces also contribute to the modulation of the epigenetic state and a variety of cell functions through distinct mechanisms that are not fully understood. Here we show that millisecond deformation of the cell nucleus caused by confinement into microfluidic channels results in wrinkling and transient disassembly of the nuclear lamina, local detachment of lamina-associated domains in chromatin and a decrease of histone methylation (histone H3 lysine 9 trimethylation) and DNA methylation. These global changes in chromatin at the early stage of cell reprogramming boost the conversion of fibroblasts into neurons and can be partially reproduced by inhibition of histone H3 lysine 9 and DNA methylation. This mechanopriming approach also triggers macrophage reprogramming into neurons and fibroblast conversion into induced pluripotent stem cells, being thus a promising mechanically based epigenetic state modulation method for cell engineering.

Original languageEnglish (US)
Pages (from-to)1191-1199
Number of pages9
JournalNature Materials
Volume21
Issue number10
DOIs
StatePublished - Oct 2022

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General Materials Science
  • Condensed Matter Physics
  • Mechanics of Materials
  • Mechanical Engineering

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