表皮质的拓缺陷决定了细胞死亡和挤出
Thuan Beng Saw1,2, Amin Doostmohammadi3, Vincent Nier4
1Mechanobiology Institute, National University of Singapore, Singapore.
Nature
|April 14, 2017
概括
皮质细胞挤出对于组织健康和癌症预防至关重要,由细胞对齐的拓缺陷驱动. 这些缺陷触发了细胞命运反应,可以被操纵,为组织再生和转移抑制提供了洞察力.
科学领域:
- 细胞生物学
- 生物物理
- 材料科学
背景情况:
- 皮质组织通过挤出去除多余的细胞, 这一过程对发育,稳态和疾病至关重要, 但其机械基础仍然不清楚.
- 细胞挤出与亡,瘤转化和过度拥挤有关,突显了它在癌症转移等病理过程中的重要性.
研究的目的:
- 探索细胞外挤的潜在机制及其与上皮组织的内在机制的联系.
- 用实验测量对表皮细胞作为活跃的阴性液晶进行模型验证.
主要方法:
- 模拟表皮细胞作为活跃的阴性液晶.
- 数字模拟与麦丁·达比犬 (MDCK) 单层细胞的应变率和应力测量进行比较.
- 通过α-catenin knockdown研究细胞间连接的作用.
- 通过几何诱导缺陷来控制挤出热点.
主要成果:
- 细胞排挤是由细胞对齐的拓缺陷 (奇点) 引发的,类似于彗星形状.
- 细胞导向场的挤出部位和脑膜缺陷之间存在普遍的相关性.
- 缺陷诱导的压力先于机械传导反应,包括YAP活性,酶-3激活和细胞挤出.
- 细胞-细胞连接的削弱减少了缺陷大小,但增加了挤出率,符合模型的预测.
结论:
- 在表皮质中自发形成的拓缺陷决定了细胞外挤和细胞命运.
- 这种缺陷驱动机制为预测体内挤出热点提供了一个框架.
- 潜在的应用包括组织再生和抑制转移,利用活性阴性液晶类比进行进一步研究.
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