PT  - JOURNAL ARTICLE
AU  - Emma Carley
AU  - Rachel M. Stewart
AU  - Abigail Zieman
AU  - Amanda Zubek
AU  - Samantha Lin
AU  - Valerie Horsley
AU  - Megan C. King
TI  - The LINC complex transmits integrin-dependent tension to the nuclear lamina and represses epidermal differentiation
AID  - 10.1101/2020.05.03.075085
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.05.03.075085
4099  - http://biorxiv.org/content/early/2020/05/04/2020.05.03.075085.short
4100  - http://biorxiv.org/content/early/2020/05/04/2020.05.03.075085.full
AB  - Cell fate decisions are essential for tissue development and homeostasis and can be induced by chemical and mechanical inputs. 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, we use the well-defined system of keratinocyte differentiation in the skin to define mechanisms by which mechanical inputs control cell fate. Although mechanical signals are known to induce epidermal differentiation, whether and how direct force transmission to the nucleus regulates cell fate decisions remains unknown. Here, we measure tension on the nucleus through the Linker of Nucleoskeleton and Cytoskeleton (LINC) complexes using a molecular biosensor during keratinocyte differentiation. We show that undifferentiated epidermal stem cells display high tension on the LINC complex when integrins are engaged. During differentiation, tension decreases on the LINC complex and on A-type lamins, suggesting that the state of the nuclear lamina is altered during differentiation. LINC complex ablation in mice reveals that LINC complexes are required to repress epidermal differentiation in vitro and in vivo, 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.Competing Interest StatementThe authors have declared no competing interest.