Author: Wang, Jing; Zhang, Yifan; Gao, Ya; Shan, Shengzhou; Li, Qingfeng
Title: EZH2 regulates the correlation between skin regeneration and the duration of mechanical stretch. Cord-id: nsd95g5r Document date: 2020_10_15
ID: nsd95g5r
Snippet: It has been widely recognized that mechanical stretch can regulate the fate of stem cells. Previous researches have shown that short-term mechanical stretch induces stem cell proliferation through activating the predominant transcription factor YAP, and YAP is a critical modulator in controlling epidermal proliferation. However, our study finds that after this phase, the cell growth arrest appears which is induced by long-term mechanical stretch. In the interfollicular epidermal stem cells (IFES
Document: It has been widely recognized that mechanical stretch can regulate the fate of stem cells. Previous researches have shown that short-term mechanical stretch induces stem cell proliferation through activating the predominant transcription factor YAP, and YAP is a critical modulator in controlling epidermal proliferation. However, our study finds that after this phase, the cell growth arrest appears which is induced by long-term mechanical stretch. In the interfollicular epidermal stem cells (IFESCs) undergoing long-term mechanical stretch in vivo and in vitro, the level of H3K27me3 and its histone methyltransferase EZH2 are significantly elevated with suppressed expression of the target genes of YAP. EZH2 forms repressive H3K27me3 that suppresses gene transcription. Small-molecule inhibitor of EZH2 rescues significantly the cell growth arrest in IFESCs induced by long-term mechanical stretch, thus promoting epidermal proliferation in vivo again. These findings reveal that there is an unexpected correlation between stem cell proliferation and the duration of mechanical stretch regulated by EZH2. This study of long-term mechanical stretch that induces the cell growth arrest provides a strategy for clinical translation to promote skin regeneration.
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