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

Cell Adhesion Cellular Reprogramming Epigenesis, Genetic Mechanotransduction, Cellular Chromatin
cell adhesion cytoskeleton direct reprogramming epigenetic state

Journal

Advanced science (Weinheim, Baden-Wurttemberg, Germany)
ISSN: 2198-3844
Titre abrégé: Adv Sci (Weinh)
Pays: Germany
ID NLM: 101664569

Informations de publication

Date de publication:
08 2023
Historique:
revised: 13 05 2023
received: 07 01 2023
medline: 29 8 2023
pubmed: 26 6 2023
entrez: 26 6 2023
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1002/advs.202300152 PMID: 37357983 PMC: PMC10460843
pubmed: 37357983
doi: 10.1002/advs.202300152
pmc: PMC10460843
doi:

Substances chimiques

Chromatin 0

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2300152

Subventions

Organisme : NIH HHS
ID : 1S10RR026866-01
Pays : United States
Organisme : NIH HHS
ID : NIHS10OD018174
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS130677
Pays : United States
Organisme : NIH HHS
ID : S10 OD025017
Pays : United States
Organisme : NIH HHS
ID : GM143485
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM143485
Pays : United States
Organisme : NIH HHS
ID : T32HL116270
Pays : United States
Organisme : NIH HHS
ID : P30CA016042
Pays : United States
Organisme : NIH HHS
ID : NS130677
Pays : United States
Organisme : NIH HHS
ID : T32AR059033
Pays : United States
Organisme : NIH HHS
ID : S10OD025017
Pays : United States
Organisme : NIH HHS
ID : S10OD025017
Pays : United States
Organisme : NIH HHS
ID : 1S10RR026866-01
Pays : United States
Organisme : NIH HHS
ID : NIHS10OD018174
Pays : United States
Organisme : NIH HHS
ID : P30CA016042
Pays : United States
Organisme : NIH HHS
ID : GM143485
Pays : United States
Organisme : NIH HHS
ID : NS130677
Pays : United States
Organisme : NIH HHS
ID : T32AR059033
Pays : United States
Organisme : NIH HHS
ID : T32HL116270
Pays : United States

Informations de copyright

© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.

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Auteurs

Jennifer Soto (J)

Department of Bioengineering, University of California, Los Angeles, CA, 90095, USA.
ORCID: 0000-0002-0014-5213

Yang Song (Y)

Department of Bioengineering, University of California, Los Angeles, CA, 90095, USA.

Yifan Wu (Y)

Department of Bioengineering, University of California, Los Angeles, CA, 90095, USA.

Binru Chen (B)

Department of Bioengineering, University of California, Los Angeles, CA, 90095, USA.

Hyungju Park (H)

Department of Molecular and Cell Biology, University of California, Berkeley, CA, 94720, USA.

Navied Akhtar (N)

Department of Biomedical Engineering, University of California, Irvine, CA, 92617, USA.

Peng-Yuan Wang (PY)

Department of Bioengineering, University of California, Los Angeles, CA, 90095, USA.
Oujiang Laboratory, Key Laboratory of Alzheimer's Disease of Zhejiang Province, Institute of Aging, Wenzhou Medical University, Wenzhou, Zhejiang, 325024, China.

Tyler Hoffman (T)

Department of Bioengineering, University of California, Los Angeles, CA, 90095, USA.

Chau Ly (C)

Department of Bioengineering, University of California, Los Angeles, CA, 90095, USA.
Department of Integrative Biology and Physiology, University of California, Los Angeles, CA, 90095, USA.

Junren Sia (J)

Department of Bioengineering, University of California, Berkeley, CA, 94720, USA.

SzeYue Wong (S)

Department of Bioengineering, University of California, Berkeley, CA, 94720, USA.

Douglas O Kelkhoff (DO)

Department of Bioengineering, University of California, Berkeley, CA, 94720, USA.

Julia Chu (J)

Department of Bioengineering, University of California, Berkeley, CA, 94720, USA.

Mu-Ming Poo (MM)

Department of Molecular and Cell Biology, University of California, Berkeley, CA, 94720, USA.

Timothy L Downing (TL)

Department of Biomedical Engineering, University of California, Irvine, CA, 92617, USA.

Amy C Rowat (AC)

Department of Bioengineering, University of California, Los Angeles, CA, 90095, USA.
Department of Integrative Biology and Physiology, University of California, Los Angeles, CA, 90095, USA.

Song Li (S)

Department of Bioengineering, University of California, Los Angeles, CA, 90095, USA.
Department of Medicine, University of California, Los Angeles, CA, 90095, USA.
Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
ORCID: 0000-0002-4760-8828

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Classifications MeSH

questionsmedicales.fr › Phénomènes physiologiques cellulaires › Adhérence cellulaire › Reduction of Intracellular Tension and Cell...
questionsmedicales.fr › Phénomènes génétiques › Reprogrammation cellulaire › Reduction of Intracellular Tension and Cell...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › Reduction of Intracellular Tension and Cell...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Mécanotransduction cellulaire › Reduction of Intracellular Tension and Cell...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Structures de chromosome › Chromatine › Reduction of Intracellular Tension and Cell...