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Transient nuclear deformation primes epigenetic state and promotes cell reprogramming.
Song, Yang; Soto, Jennifer; Chen, Binru; Hoffman, Tyler; Zhao, Weikang; Zhu, Ninghao; Peng, Qin; Liu, Longwei; Ly, Chau; Wong, Pak Kin; Wang, Yingxiao; Rowat, Amy C; Kurdistani, Siavash K; Li, Song.
Afiliación
  • Song Y; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA.
  • Soto J; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA.
  • Chen B; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA.
  • Hoffman T; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA.
  • Zhao W; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA.
  • Zhu N; Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, USA.
  • Peng Q; Department of Bioengineering, University of California San Diego, San Diego, CA, USA.
  • Liu L; Department of Bioengineering, University of California San Diego, San Diego, CA, USA.
  • Ly C; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA.
  • Wong PK; Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, USA.
  • Wang Y; Department of Bioengineering, University of California San Diego, San Diego, CA, USA.
  • Rowat AC; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA.
  • Kurdistani SK; Department of Integrative Biology & Physiology, University of California Los Angeles, Los Angeles, CA, USA.
  • Li S; Department of Biological Chemistry, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Nat Mater ; 21(10): 1191-1199, 2022 10.
Article en En | MEDLINE | ID: mdl-35927431
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.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Histonas / Reprogramación Celular Idioma: En Año: 2022 Tipo del documento: Article
Texto completo
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Histonas / Reprogramación Celular Idioma: En Año: 2022 Tipo del documento: Article