Intercellular Adhesion-Dependent Cell Survival and ROCK-Regulated Actomyosin-Driven Forces Mediate Self-Formation of a Retinal Organoid.
Intercellular Adhesion-Dependent Cell Survival and ROCK-Regulated Actomyosin-Driven Forces Mediate Self-Formation of a Retinal Organoid.
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DOI：
10.1016/j.stemcr.2016.03.011
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发表时间：
2016-05-10
影响因子：
5.9
通讯作者：
Liu W
中科院分区：
文献类型：
--
作者：
Lowe A;Harris R;Bhansali P;Cvekl A;Liu W
在这项研究中，我们剖析了人胚胎干细胞（hESC）来源的培养物中视网膜类器官的形态发生，并建立了一种分离大量视网膜类器官以模拟人视网膜发育和疾病的便捷方法。通过基质胶/hESC 团块的漂浮培养产生上皮化囊肿。囊肿自发附着和扩散后，形成具有紧密连接的图案化视网膜单层。分散酶介导的单层分离和随后的漂浮培养导致视网膜类器官的自我形成，包括图案化的神经视网膜、睫状缘和视网膜色素上皮。自组织需要细胞间粘附依赖性细胞存活和 ROCK 调节的肌动球蛋白驱动力。我们的数据支持这样一种假设，即新指定的神经视网膜祖细胞通过最小化细胞表面张力形成平衡的特征结构。在长期培养中，视网膜类器官自主生成分层视网膜组织，包括具有外节超微结构的光感受器。我们的系统需要最少的手动操作，已在两个人类多能干细胞系中得到验证，并提供了体内视杯内陷的见解。建立了一种从 hESC 中分离大量视网膜类器官的方法 分散酶介导的细胞脱离导致视网膜类器官的自我形成 漂浮培养物中的细胞间粘附是细胞生存所必需的 自组织需要 ROCK 调节的肌动球蛋白驱动力 Liu 及其同事建立了一种从 hESC 中分离大量视网膜类器官的方法。视网膜类器官在分散酶介导的视网膜单层分离和随后的漂浮培养后自发形成。细胞间粘附依赖性细胞存活和 ROCK 调节的肌动球蛋白驱动力介导自组织。他们提出了一个假设——新指定的神经视网膜祖细胞通过最小化细胞表面张力形成平衡的特征结构。
In this study we dissected retinal organoid morphogenesis in human embryonic stem cell (hESC)-derived cultures and established a convenient method for isolating large quantities of retinal organoids for modeling human retinal development and disease. Epithelialized cysts were generated via floating culture of clumps of Matrigel/hESCs. Upon spontaneous attachment and spreading of the cysts, patterned retinal monolayers with tight junctions formed. Dispase-mediated detachment of the monolayers and subsequent floating culture led to self-formation of retinal organoids comprising patterned neuroretina, ciliary margin, and retinal pigment epithelium. Intercellular adhesion-dependent cell survival and ROCK-regulated actomyosin-driven forces are required for the self-organization. Our data supports a hypothesis that newly specified neuroretina progenitors form characteristic structures in equilibrium through minimization of cell surface tension. In long-term culture, the retinal organoids autonomously generated stratified retinal tissues, including photoreceptors with ultrastructure of outer segments. Our system requires minimal manual manipulation, has been validated in two lines of human pluripotent stem cells, and provides insight into optic cup invagination in vivo. Established a method for isolating large amounts of retinal organoids from hESCs Dispase-mediated cell detachment led to self-formation of the retinal organoids Intercellular adhesions in the floating cultures are required for cell survival ROCK-regulated actomyosin-driven forces are required for the self-organization Liu and colleagues established a method for isolating large quantities of retinal organoids from hESCs. The retinal organoids spontaneously formed upon Dispase-mediated detachment of retinal monolayers and subsequent floating culture. Intercellular adhesion-dependent cell survival and ROCK-regulated actomyosin-driven forces mediate the self-organization. They propose a hypothesis—newly specified neuroretina progenitors form characteristic structures in equilibrium through minimization of cell surface tension.