Cell volume regulates terminal differentiation of cultured human epidermal keratinocytes.

IF 3.6 3区 生物学 Q3 CELL BIOLOGY
Journal of cell science Pub Date : 2025-09-01 Epub Date: 2025-09-08 DOI:10.1242/jcs.264242
Sebastiaan Zijl, Toru Hiratsuka, Atefeh Mobasseri, Mirsana Ebrahimkutty, Mandy Börmel, Sergi Garcia-Manyes, Fiona M Watt
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引用次数: 0

Abstract

To gain insights into the human epidermal stem cell niche, we have previously identified micron-scale topographical substrates that regulate differentiation of spread keratinocytes. On one substrate (S1), cells interact with circular topographies and differentiation is stimulated; on the other (S2), cells interact with triangular topographies and differentiation is inhibited. Cell stiffness on S1 and S2 was similar, and nuclear localisation of the mechano-sensitive transcriptional regulator YAP1 was decreased on S1 and S2 compared to on flat substrates. However, cells on S2 exhibited reduced cell volume, leading us to explore the potential for volume-regulated differentiation. Treatment with polyethylene glycol decreased cell volume and inhibited differentiation under a range of conditions. Conversely, deionized water increased cell volume and stimulated differentiation. Bulk RNA sequencing identified several substrate-responsive genes, including aquaporins and ion channels. A membrane permeable Ca2+ chelator and an inhibitor of the water channel aquaporin 3 blocked volume-induced differentiation. These studies identify cell volume as a mechanism by which keratinocyte-niche interactions regulate terminal differentiation.

细胞体积调节培养的人表皮角质形成细胞的终末分化。
为了深入了解人类表皮干细胞的生态位,我们之前已经确定了调节扩散角化细胞分化的微米尺度的地形底物。在一个底物(S1)上,细胞与圆形地形相互作用,并刺激分化;另一方面(S2),细胞与三角形地形相互作用,分化受到抑制。S1和S2的细胞刚度相似;与平面底物相比,机械敏感转录调控因子YAP1在S1和S2上的核定位降低。然而,S2上的细胞表现出细胞体积减小,这促使我们探索潜在的体积调节分化。在一系列条件下,聚乙二醇处理可减少细胞体积并抑制分化。相反,去离子水增加细胞体积并刺激分化。大量RNA测序鉴定了几个底物反应基因,包括水通道蛋白和离子通道。膜渗透性Ca2+螯合剂和水通道水通道蛋白3抑制剂阻断了体积诱导的分化。这些研究确定细胞体积是角化细胞-生态位相互作用调节终端分化的机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of cell science
Journal of cell science 生物-细胞生物学
CiteScore
7.30
自引率
2.50%
发文量
393
审稿时长
1.4 months
期刊介绍: Journal of Cell Science publishes cutting-edge science, encompassing all aspects of cell biology.
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