机械化学回路推动皮肤器官样体的自组织。
The mechano-chemical circuit drives skin organoid self-organization.
发表日期:2023 Sep 05
作者:
Mingxing Lei, Hans I-Chen Harn, Qiwei Li, Jingwei Jiang, Wang Wu, Wei Zhou, Tin-Xin Jiang, Mengyue Wang, Jinwei Zhang, Yung-Chih Lai, Wen-Tau Juan, Randall Bruce Widelitz, Li Yang, Zhong-Ze Gu, Cheng-Ming Chuong
来源:
Stem Cell Research & Therapy
摘要:
器官样体中的干细胞通过未知的机制自组织成组织模式。在此,我们利用皮肤样体来分析这一过程。细胞行为视频显示,从具有形态发生能力的多个球状单位(CMU)向平面皮肤的形态转化特点是在平静之前出现两次突然的细胞运动增加事件。自组织过程受到由分子传感器、调节物和执行物组成的造形模块的控制。逐渐增加的真皮硬度提供了初始的驱动力(驱动器),激活表皮囊的Yap1(传感器)。表皮囊中的Notch信号(调节物1)调节了Yap1激活的阈值。激活的Yap1在基底细胞中诱导了Wnt和MMPs(表皮执行物),促进细胞流动,使表皮细胞从CMU中突出出来。真皮细胞表达的Rock(真皮执行物)在两个CMU之间生成了一个坚硬的力桥,并通过激活Laminin和β1整合素加速组织混合。因此,这个自组织合并过程由一个机械-化学回路控制。超越皮肤,器官样体中的自组织可能使用类似的机械-化学回路结构。
Stem cells in organoids self-organize into tissue patterns with unknown mechanisms. Here, we use skin organoids to analyze this process. Cell behavior videos show that the morphological transformation from multiple spheroidal units with morphogenesis competence (CMU) to planar skin is characterized by two abrupt cell motility-increasing events before calming down. The self-organizing processes are controlled by a morphogenetic module composed of molecular sensors, modulators, and executers. Increasing dermal stiffness provides the initial driving force (driver) which activates Yap1 (sensor) in epidermal cysts. Notch signaling (modulator 1) in epidermal cyst tunes the threshold of Yap1 activation. Activated Yap1 induces Wnts and MMPs (epidermal executers) in basal cells to facilitate cellular flows, allowing epidermal cells to protrude out from the CMU. Dermal cell-expressed Rock (dermal executer) generates a stiff force bridge between two CMU and accelerates tissue mixing via activating Laminin and β1-integrin. Thus, this self-organizing coalescence process is controlled by a mechano-chemical circuit. Beyond skin, self-organization in organoids may use similar mechano-chemical circuit structures.