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The LINC complex transmits integrin-dependent tension to the nuclear lamina and represses epidermal differentiation

by Zubek, Amanda , King, Diane E , Stewart, Rachel M , Carley, Emma , King, Megan C , Horsley, Valerie , Zieman, Abigail , Jalilian, Iman , Lin, Samantha

in Animals / Biosensors / Cell Biology / Cell Differentiation / Cell fate / Cytoskeleton / differentiation / epidermis / Epidermis - physiology / Experiments / Extracellular matrix / Female / Gene expression / Integrins / Integrins - metabolism / Lamin Type A - metabolism / Lamins / LINC complex / Mechanotransduction / Mechanotransduction, Cellular - physiology / Mice / nuclear lamina / Nuclear Lamina - physiology / Plakins - genetics / Plakins - metabolism / Progenitor cells / Scientific equipment and supplies industry / Sensors / Skin / stem cell / Stem cell transplantation / Stem cells / Stem Cells and Regenerative Medicine

2021

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The LINC complex transmits integrin-dependent tension to the nuclear lamina and represses epidermal differentiation

by Zubek, Amanda , King, Diane E , Stewart, Rachel M , Carley, Emma , King, Megan C , Horsley, Valerie , Zieman, Abigail , Jalilian, Iman , Lin, Samantha

2021

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The LINC complex transmits integrin-dependent tension to the nuclear lamina and represses epidermal differentiation

by Zubek, Amanda , King, Diane E , Stewart, Rachel M , Carley, Emma , King, Megan C , Horsley, Valerie , Zieman, Abigail , Jalilian, Iman , Lin, Samantha

2021

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Journal Article

The LINC complex transmits integrin-dependent tension to the nuclear lamina and represses epidermal differentiation

Zubek, Amanda,

King, Diane E,

Stewart, Rachel M,

Carley, Emma,

King, Megan C,

Horsley, Valerie,

Zieman, Abigail,

Jalilian, Iman,

Lin, Samantha

2021

Overview

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.

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Publisher

eLife Science Publications, Ltd,eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd

Subject

Animals

/ Biosensors

/ Cell Biology

/ Cell Differentiation

/ Cell fate

/ Cytoskeleton

/ differentiation