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The LINC complex transmits integrin-dependent tension to the nuclear lamina and represses epidermal differentiation
While the mechanisms by which chemical signals control cell fate have been well studied, the impact of mechanical inputs on cell fate decisions is not well understood. Here, using the well-defined system of keratinocyte differentiation in the skin, we examine whether and how direct force transmissio...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051949/ https://www.ncbi.nlm.nih.gov/pubmed/33779546 http://dx.doi.org/10.7554/eLife.58541 |
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author | Carley, Emma Stewart, Rachel M Zieman, Abigail Jalilian, Iman King, Diane E Zubek, Amanda Lin, Samantha Horsley, Valerie King, Megan C |
author_facet | Carley, Emma Stewart, Rachel M Zieman, Abigail Jalilian, Iman King, Diane E Zubek, Amanda Lin, Samantha Horsley, Valerie King, Megan C |
author_sort | Carley, Emma |
collection | PubMed |
description | While the mechanisms by which chemical signals control cell fate have been well studied, the impact of mechanical inputs on cell fate decisions is 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. |
format | Online Article Text |
id | pubmed-8051949 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-80519492021-04-21 The LINC complex transmits integrin-dependent tension to the nuclear lamina and represses epidermal differentiation Carley, Emma Stewart, Rachel M Zieman, Abigail Jalilian, Iman King, Diane E Zubek, Amanda Lin, Samantha Horsley, Valerie King, Megan C eLife Cell Biology While the mechanisms by which chemical signals control cell fate have been well studied, the impact of mechanical inputs on cell fate decisions is 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. eLife Sciences Publications, Ltd 2021-03-29 /pmc/articles/PMC8051949/ /pubmed/33779546 http://dx.doi.org/10.7554/eLife.58541 Text en © 2021, Carley et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cell Biology Carley, Emma Stewart, Rachel M Zieman, Abigail Jalilian, Iman King, Diane E Zubek, Amanda Lin, Samantha Horsley, Valerie King, Megan C The LINC complex transmits integrin-dependent tension to the nuclear lamina and represses epidermal differentiation |
title | The LINC complex transmits integrin-dependent tension to the nuclear lamina and represses epidermal differentiation |
title_full | The LINC complex transmits integrin-dependent tension to the nuclear lamina and represses epidermal differentiation |
title_fullStr | The LINC complex transmits integrin-dependent tension to the nuclear lamina and represses epidermal differentiation |
title_full_unstemmed | The LINC complex transmits integrin-dependent tension to the nuclear lamina and represses epidermal differentiation |
title_short | The LINC complex transmits integrin-dependent tension to the nuclear lamina and represses epidermal differentiation |
title_sort | linc complex transmits integrin-dependent tension to the nuclear lamina and represses epidermal differentiation |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051949/ https://www.ncbi.nlm.nih.gov/pubmed/33779546 http://dx.doi.org/10.7554/eLife.58541 |
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