Mechanical strain treatment improves nuclear transfer reprogramming efficiency by enhancing chromatin accessibility.
Mechanical strain treatment improves nuclear transfer reprogramming efficiency by enhancing chromatin accessibility.
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DOI：
10.1016/j.stemcr.2023.02.007
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发表时间：
2023-04-11
影响因子：
5.9
通讯作者：
Zhang, Yong
中科院分区：
文献类型：
--
作者：
Chen, Yujie;Xu, Ruimin;Zhou, Shuang;Zhao, Chengchen;Hu, Ziyue;Hua, Yuwei;Xiong, Yanhong;Liu, Xiaoyu;Lu, Junhong;Sun, Yao;Li, Chong;Gao, Shaorong;Zhang, Yong
细胞力学性质被认为是影响细胞命运转换的重要因素，但细胞力学性质与转换效率和染色质结构之间的联系仍然难以捉摸。在这里，我们预测，机械应变处理可以诱导细胞的去分化和转分化的签名，我们验证了这一预测表明，机械应变处理的小鼠卵丘细胞（CC）表现出显着提高体细胞核移植（SCNT）重编程效率。我们发现，CC的染色质可及性在整体上增加了机械应变处理，这种增加部分介导的诱导YAP-TEAD相互作用。此外，使用机械应变处理的CC可以防止SCNT胚胎中的转录失调。综上所述，我们的研究结果表明，调节细胞的机械性能，以调节表观遗传状态是一种有前途的方法，以促进细胞命运的转变。机械性能的调节可以促进有效的SCNT机械增强的染色质重塑影响细胞命运重编程潜在的ms-SCNT胚胎部分修复EGA中的失调基因一种综合方法来评估机械诱导的转变的后果Chen et al.提供了一种综合的方法来解决如何澄清机械性能和细胞命运转变的可量化调制之间的关系的问题，包括机械操作，过渡后果的快速检查，和高通量表观遗传学评价。他们首先报道，调节适当的细胞外力可以显著增加染色质可及性并有效促进体细胞核移植（SCNT），这表明染色质重塑在连接机械处理反应和细胞命运重编程潜力方面起着介导作用。
Cellular mechanical properties are considered to be important factors affecting cell fate transitions, but the links between cellular mechanical properties and transition efficiency and chromatin structure remain elusive. Here, we predicted that mechanical strain treatment could induce signatures of cellular dedifferentiation and transdifferentiation, and we validated this prediction by showing that mechanical strain-treated mouse cumulus cells (CCs) exhibit significantly improved somatic cell nuclear transfer (SCNT) reprogramming efficiency. We found that the chromatin accessibility of CCs was globally increased by mechanical strain treatment and that this increase was partially mediated by the induction of the YAP-TEAD interaction. Moreover, using mechanical strain-treated CCs could prevent transcriptional dysregulation in SCNT embryos. Taken together, our study results demonstrated that modulating cell mechanical properties to regulate epigenetic status is a promising approach to facilitate cell fate transition. Modulation of mechanical properties can facilitate efficient SCNT Mechanically enhanced chromatin remodeling affects cell fate reprogramming potential ms-SCNT embryos partially repaired dysregulated genes in EGA An integrative approach to evaluate the consequences of mechanical-induced transition Chen et al. provide an integrative approach to address the question of how to clarify the relationship between the quantifiable modulation of mechanical properties and cell fate transitions, including mechanical manipulation, rapid examination of transition consequences, and high-throughput epigenetic evaluation. They first report that modulation of an appropriate extracellular force can dramatically increase chromatin accessibility and effectively facilitate somatic cell nuclear transfer (SCNT), indicating that chromatin remodeling plays a mediating role in linking the response to mechanical treatment and cell fate reprogramming potential.
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