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LINC 复合物将整合素依赖性张力传递到核层并抑制表皮分化。

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

机构信息

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.

出版信息

Elife. 2021 Mar 29;10:e58541. doi: 10.7554/eLife.58541.

DOI:10.7554/eLife.58541
PMID:33779546
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8051949/
Abstract

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.

摘要

虽然化学信号控制细胞命运的机制已经得到了很好的研究，但机械输入对细胞命运决定的影响还不是很清楚。在这里，我们使用皮肤中角质形成细胞分化这一明确的系统，研究直接向细胞核传递力是否以及如何调节表皮细胞命运。我们使用分子生物传感器发现，通过核骨架和细胞骨架连接物（LINC）复合物施加在细胞核上的张力需要整联蛋白在未分化的表皮干细胞中的参与，并且在分化过程中伴随着 A 型层粘连蛋白张力的降低而释放。在小鼠中 LINC 复合物的缺失表明，LINC 复合物在体内和体外抑制表皮分化是必需的，并影响表皮分化基因的可及性，这表明整合素与细胞核之间的力转导在维持角质形成细胞祖细胞中发挥作用。这项工作揭示了一种直接的机械转导途径，能够传递粘附特异性信号来调节细胞命运。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d8/8051949/f088e0068a29/elife-58541-fig6.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d8/8051949/02c6c798781a/elife-58541-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d8/8051949/536765b1d4ae/elife-58541-fig4-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d8/8051949/2f5f32b77fee/elife-58541-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d8/8051949/8d6b3e7cfe30/elife-58541-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d8/8051949/1ba9a5f2315e/elife-58541-fig5-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d8/8051949/f088e0068a29/elife-58541-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d8/8051949/6949f5215521/elife-58541-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d8/8051949/ebd904032397/elife-58541-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d8/8051949/aaf87e5be777/elife-58541-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d8/8051949/deecfba2e80a/elife-58541-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d8/8051949/e918453039f4/elife-58541-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d8/8051949/7e166a50a311/elife-58541-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d8/8051949/4ff27f706fa9/elife-58541-fig3-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d8/8051949/2c11260fa01b/elife-58541-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d8/8051949/02c6c798781a/elife-58541-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d8/8051949/536765b1d4ae/elife-58541-fig4-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d8/8051949/2f5f32b77fee/elife-58541-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d8/8051949/8d6b3e7cfe30/elife-58541-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d8/8051949/1ba9a5f2315e/elife-58541-fig5-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d8/8051949/f088e0068a29/elife-58541-fig6.jpg

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4
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