小柯机器人

研究揭示拉伸调控皮肤扩张的机制
2020-07-30 14:36

比利时布鲁塞尔自由大学Cédric Blanpain和英国剑桥大学Benjamin D. Simons小组合作,发现了单细胞水平揭示拉伸调控皮肤扩张的机制。相关论文在线发表在2020年7月29日出版的《自然》杂志上。

研究人员构建了一种小鼠模型,其可以在单细胞水平研究皮肤表皮拉伸的后果。利用克隆分析与定量建模和单细胞RNA测序相结合的多学科方法,研究人员发现拉伸可通过在表皮干细胞更新时产生瞬时偏倚来诱导皮肤扩张,而基底祖细胞的第二个亚群仍致力于分化。

利用转录和染色质分析,研究人员确定了如何通过拉伸来调节细胞状态和基因调控网络。使用药物抑制剂和小鼠突变体,研究人员阐明了在体内单细胞水平上拉伸介导组织扩张的机制。

据介绍,重建手术充分利用了皮肤响应拉伸生长的能力。尽管已经在体外研究了表皮细胞对拉伸的响应,但尚不清楚机械力如何影响其在体内的行为。

附:英文原文

Title: Mechanisms of stretch-mediated skin expansion at single-cell resolution

Author: Mariaceleste Aragona, Alejandro Sifrim, Milan Malfait, Yura Song, Jens Van Herck, Sophie Dekoninck, Souhir Gargouri, Galle Lapouge, Benjamin Swedlund, Christine Dubois, Pieter Baatsen, Katlijn Vints, Seungmin Han, Fadel Tissir, Thierry Voet, Benjamin D. Simons, Cdric Blanpain

Issue&Volume: 2020-07-29

Abstract: The ability of the skin to grow in response to stretching has been exploited in reconstructive surgery1. Although the response of epidermal cells to stretching has been studied in vitro2,3, it remains unclear how mechanical forces affect their behaviour in vivo. Here we develop a mouse model in which the consequences of stretching on skin epidermis can be studied at single-cell resolution. Using a multidisciplinary approach that combines clonal analysis with quantitative modelling and single-cell RNA sequencing, we show that stretching induces skin expansion by creating a transient bias in the renewal activity of epidermal stem cells, while a second subpopulation of basal progenitors remains committed to differentiation. Transcriptional and chromatin profiling identifies how cell states and gene-regulatory networks are modulated by stretching. Using pharmacological inhibitors and mouse mutants, we define the step-by-step mechanisms that control stretch-mediated tissue expansion at single-cell resolution in vivo. Single-cell analysis in a mouse model of skin stretching shows that stretching causes a transient expansion bias in a population of epidermal stem cells, which is associated with chromatin remodelling and changes in transcriptional profile