The LINC complex transmits integrin-dependent tension to the nuclear lamina and represses epidermal differentiation
- Yale School of Medicine, United States
- Yale University, United States
Abstract
While the mechanisms by which chemical signals control cell fate have been well studied, how mechanical inputs impact cell fate decisions are not well understood. Here, using the well-defined system of keratinocyte differentiation in the skin, we examine whether and how direct force transmission to the nucleus regulates epidermal cell fate. Using a molecular biosensor, we find that tension on the nucleus through Linker of Nucleoskeleton and Cytoskeleton (LINC) complexes requires integrin engagement in undifferentiated epidermal stem cells, and is released during differentiation concomitant with decreased tension on A-type lamins. LINC complex ablation in mice reveals that LINC complexes are required to repress epidermal differentiation in vivo and in vitro and influence accessibility of epidermal differentiation genes, suggesting that force transduction from engaged integrins to the nucleus plays a role in maintaining keratinocyte progenitors. This work reveals a direct mechanotransduction pathway capable of relaying adhesion-specific signals to regulate cell fate.
Data availability
Sequencing data have been deposited as a single BioProject at NCBI with accession number PRJNA636991
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Regulation of epidermal differentiation by the LINC complexNCBI BioProject, PRJNA636991.
Article and author information
Author details
Funding
National Institutes of Health (R01 GM129308)
- Emma Carley
- Iman Jalilian
- Megan C King
American Heart Association (16PRE27460000)
- Rachel Stewart
Ludwig Family Foundation
- Rachel Stewart
- Megan C King
National Institutes of Health (R01 AR060295)
- Valerie Horsley
National Institutes of Health (R01 AR069550)
- Valerie Horsley
National Institutes of Health (T32 AR007016)
- Abigail G Zieman
National Institutes of Health (T32 GM007223)
- Emma Carley
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Elaine Fuchs, Howard Hughes Medical Institute, The Rockefeller University, United States
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animal care and experimental procedures were conducted in accord with requirements approved by the Institutional Animal Care and Use Committee of Yale University. IACUC Approval 2018-11248.
Version history
- Received: May 5, 2020
- Accepted: March 26, 2021
- Accepted Manuscript published: March 29, 2021 (version 1)
- Version of Record published: April 16, 2021 (version 2)
- Version of Record updated: January 18, 2024 (version 3)
Copyright
© 2021, Carley et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The LINC complex transmits integrin-dependent tension to the nuclear lamina and represses epidermal differentiation
eLife 10:e58541.
https://doi.org/10.7554/eLife.58541
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