多能干细胞诱导晶状体祖细胞和晶状体小体:人晶状体发育和眼疾发病机制的新工具。
Generation of Lens Progenitor Cells and Lentoid Bodies from Pluripotent Stem Cells: Novel Tools for Human Lens Development and Ocular Disease Etiology.
机构信息
Departments Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
出版信息
Cells. 2022 Nov 6;11(21):3516. doi: 10.3390/cells11213516.
In vitro differentiation of human pluripotent stem cells (hPSCs) into specialized tissues and organs represents a powerful approach to gain insight into those cellular and molecular mechanisms regulating human development. Although normal embryonic eye development is a complex process, generation of ocular organoids and specific ocular tissues from pluripotent stem cells has provided invaluable insights into the formation of lineage-committed progenitor cell populations, signal transduction pathways, and self-organization principles. This review provides a comprehensive summary of recent advances in generation of adenohypophyseal, olfactory, and lens placodes, lens progenitor cells and three-dimensional (3D) primitive lenses, "lentoid bodies", and "micro-lenses". These cells are produced alone or "community-grown" with other ocular tissues. Lentoid bodies/micro-lenses generated from human patients carrying mutations in crystallin genes demonstrate proof-of-principle that these cells are suitable for mechanistic studies of cataractogenesis. Taken together, current and emerging advanced in vitro differentiation methods pave the road to understand molecular mechanisms of cataract formation caused by the entire spectrum of mutations in DNA-binding regulatory genes, such as PAX6, SOX2, FOXE3, MAF, PITX3, and HSF4, individual crystallins, and other genes such as BFSP1, BFSP2, EPHA2, GJA3, GJA8, LIM2, MIP, and TDRD7 represented in human cataract patients.
人多能干细胞(hPSCs)体外分化为特化组织和器官代表了一种强大的方法,可以深入了解那些调节人类发育的细胞和分子机制。尽管正常的胚胎眼发育是一个复杂的过程,但多能干细胞衍生的眼类器官和特定眼组织为谱系定向祖细胞群体、信号转导途径和自我组织原则的形成提供了宝贵的见解。本综述全面总结了近年来在腺垂体、嗅觉和晶状体基板、晶状体祖细胞和三维(3D)原始晶状体、“晶状体小体”和“微晶状体”生成方面的最新进展。这些细胞单独产生或与其他眼组织“共同生长”。携带晶体蛋白基因突变的人类患者产生的晶状体小体/微晶状体证明了这些细胞适合用于研究晶体蛋白基因突变引起白内障形成的机制。总之,目前和新兴的体外分化方法为理解由 PAX6、SOX2、FOXE3、MAF、PITX3 和 HSF4 等 DNA 结合调节基因、单个晶体蛋白以及 BFSP1、BFSP2、EPH A2、GJA3、GJA8、LIM2、MIP 和 TDRD7 等其他基因的整个突变谱引起的白内障形成的分子机制铺平了道路。