Rapid Differentiation of Multi-Zone Ocular Cells from Human Induced Pluripotent Stem Cells and Generation of Corneal Epithelial and Endothelial Cells
Rapid Differentiation of Multi-Zone Ocular Cells from Human Induced Pluripotent Stem Cells and Generation of Corneal Epithelial and Endothelial Cells
复制标题
人诱导多能干细胞快速分化多区眼细胞并生成角膜上皮和内皮细胞
DOI：
10.1089/scd.2018.0176
复制
发表时间：
2019-04-01
影响因子：
4
通讯作者：
Shi, Weiyun
中科院分区：
文献类型：
--
作者：
Li, Zongyi;Duan, Haoyun;Shi, Weiyun
眼睛是一个具有高度特化组织结构的复杂器官。人多能干细胞（human pluripotent stem cells，hPSC）的建立使得能够在体外模拟眼发育。大多数hPSC衍生的眼细胞的分化工作集中在单一的组织特异性谱系上，然而，这在反映眼发育的复杂性方面面临困难。最近，一个自我形成的外胚层自主多区眼细胞的产生有效地模仿整个眼睛的发育过程。在这项研究中，我们开发了一种快速确定的方法来诱导多区眼细胞（MZOCs）从人诱导多能干细胞，这具体经历了前神经外胚层和眼区干细胞的关键祖细胞阶段的2.5维培养。这些分化的细胞类型跨越神经视网膜、视网膜色素上皮、表面外胚层、神经嵴和透镜细胞。此外，MZOC的表面外胚层区可被机械分离并诱导为角膜上皮细胞，分离的神经嵴区可定向为角膜内皮细胞。这种体外分化过程生动地模拟了脊椎动物眼的发育过程，为眼形态发生的研究提供了一个有前途的模型，也为角膜再生医学提供了理想的种子细胞来源。
Eye is a complex organ with a highly specialized tissue structure. The establishment of human pluripotent stem cells (hPSCs) has allowed the simulation of eye development in vitro. Most differentiation works of hPSC-derived ocular cells focus on a single, tissue-specific lineage, however, that faces difficulty in reflecting the complexity of eye development. Recently, the generation of a self-formed ectodermal autonomous multi-zone of ocular cells availably mimics the process of whole-eye development. In this study, we developed a rapid defined method to induce the differentiation of multi-zone ocular cells (MZOCs) from human induced pluripotent stem cells, which specifically experienced the key progenitor stages of anterior neuroectoderm and eye field stem cells by a 2.5-dimensional culture. These differentiated cell types spanned neural retina, retinal pigment epithelium, surface ectoderm, and neural crest and lens cells. In addition, the surface ectoderm zone of MZOCs could be mechanically isolated and induced into corneal epithelial cells, and the isolated neural crest zone could be directed into corneal endothelial cells. This in vitro differentiation process vividly mimics the development of vertebrate eye, and it provides a promising model for the study of ocular morphogenesis, as well as an ideal resource of seed cells for corneal regenerative medicine.