The ability of the skin to grow in response to stretching has been exploited in reconstructive surgery 1 . Although the response of epidermal cells to stretching has been studied in vitro 2 , 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 profiles.

中文翻译：

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单细胞分辨率下拉伸介导的皮肤扩张机制

皮肤因拉伸而生长的能力已被用于重建手术 1。尽管已在体外研究了表皮细胞对拉伸的反应 2、3，但尚不清楚机械力如何影响它们在体内的行为。在这里，我们开发了一个小鼠模型，其中可以在单细胞分辨率下研究拉伸对皮肤表皮的影响。使用将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，我们表明拉伸通过在表皮干细胞的更新活动中产生瞬时偏差来诱导皮肤扩张，而基底祖细胞的第二个亚群仍然致力于分化. 转录和染色质分析确定了细胞状态和基因调控网络如何通过拉伸进行调节。使用药理学抑制剂和小鼠突变体，我们定义了在体内以单细胞分辨率控制拉伸介导的组织扩张的分步机制。皮肤拉伸小鼠模型中的单细胞分析表明，拉伸会导致表皮干细胞群出现短暂的扩张偏差，这与染色质重塑和转录谱的变化有关。