In situ modulation of intestinal organoid epithelial curvature through photoinduced viscoelasticity directs crypt morphogenesis.
In situ modulation of intestinal organoid epithelial curvature through photoinduced viscoelasticity directs crypt morphogenesis.
复制标题
DOI：
10.1126/sciadv.add5668
复制
发表时间：
2023-01-20
期刊：
影响因子：
13.6
通讯作者：
中科院分区：
文献类型：
--
作者：
时空协调转换上皮曲率是必要的，以产生隐窝绒毛结构在肠道发育。然而，驱动隐窝形态发生的机械转导通路的时间调节仍然研究不足。肠类器官已被证明可用于体外研究隐窝形态发生，但对静态培养支架的依赖限制了评估曲率变化的时间效应的能力。在这里，光诱导的水凝胶交联交换反应是用来时空改变上皮曲率和曲率的动态变化如何影响mechanotransduction途径，以指导隐窝形态发生研究。光图案化曲率增加膜张力和去极化，这是随后的核定位的yes相关蛋白1（雅普）所需的曲率变化后24小时观察。曲率导向的隐窝形态发生后，只发生在诱导分化的延迟，与空间限制的雅普本地化的延迟相一致，表明曲率的动态变化启动上皮曲率依赖性mechanotransduction途径，暂时调节隐窝形态发生。肠类器官弯曲的时空模式激活调节隐窝形成的机械转导途径。
Spatiotemporally coordinated transformations in epithelial curvature are necessary to generate crypt-villus structures during intestinal development. However, the temporal regulation of mechanotransduction pathways that drive crypt morphogenesis remains understudied. Intestinal organoids have proven useful to study crypt morphogenesis in vitro, yet the reliance on static culture scaffolds limits the ability to assess the temporal effects of changing curvature. Here, a photoinduced hydrogel cross-link exchange reaction is used to spatiotemporally alter epithelial curvature and study how dynamic changes in curvature influence mechanotransduction pathways to instruct crypt morphogenesis. Photopatterned curvature increased membrane tension and depolarization, which was required for subsequent nuclear localization of yes-associated protein 1 (YAP) observed 24 hours following curvature change. Curvature-directed crypt morphogenesis only occurred following a delay in the induction of differentiation that coincided with the delay in spatially restricted YAP localization, indicating that dynamic changes in curvature initiate epithelial curvature–dependent mechanotransduction pathways that temporally regulate crypt morphogenesis. Spatiotemporal patterning of curvature in intestinal organoids activates mechanotransduction pathways that regulate crypt formation.
登录
查看更多内容
影响因子：
5.5
作者：
Kwon O;Han TS;Son MY
通讯作者：
Son MY
影响因子：
19.6
作者：
Luciano, Marine;Xue, Shi-Lei;Gabriele, Sylvain
通讯作者：
Gabriele, Sylvain
影响因子：
10
作者：
Hushka, Ella A.;Yavitt, F. Max;Anseth, Kristi S.
通讯作者：
Anseth, Kristi S.
影响因子：
64.8
作者：
Gregorieff, Alex;Liu, Yu;Wrana, Jeffrey L.
通讯作者：
Wrana, Jeffrey L.
影响因子：
2.7
作者：
Alexandrakis, V.;Niarchos, D.;Panagiotopoulos, I.
通讯作者：
Panagiotopoulos, I.