eLife | |
The LINC complex transmits integrin-dependent tension to the nuclear lamina and represses epidermal differentiation | |
Emma Carley1  Rachel M Stewart1  Iman Jalilian1  Megan C King2  Amanda Zubek3  Abigail Zieman4  Samantha Lin4  Valerie Horsley5  Diane E King6  | |
[1] Department of Cell Biology, Yale School of Medicine, New Haven, United States;Department of Cell Biology, Yale School of Medicine, New Haven, United States;Department of Molecular, Cell and Developmental Biology, Yale University, New Haven, United States;Department of Dermatology, Yale School of Medicine, New Haven, United States;Department of Molecular, Cell and Developmental Biology, Yale University, New Haven, United States;Department of Molecular, Cell and Developmental Biology, Yale University, New Haven, United States;Department of Dermatology, Yale School of Medicine, New Haven, United States;Sunnycrest Bioinformatics, Flemington, United States; | |
关键词: epidermis; stem cell; differentiation; mechanotransduction; nuclear lamina; LINC complex; Mouse; | |
DOI : 10.7554/eLife.58541 | |
来源: eLife Sciences Publications, Ltd | |
【 摘 要 】
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.
【 授权许可】
CC BY
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
RO202104269367926ZK.pdf | 2918KB | download |