Functional microglia derived from human pluripotent stem cells empower retinal organs

作     者：Mei-Ling Gao Xiao Zhang Fang Han Jia Xu Si-Jian Yu Kangxin Jin Zi-Bing Jin Mei-Ling Gao;Xiao Zhang;Fang Han;Jia Xu;Si-Jian Yu;Kangxin Jin;Zi-Bing Jin

作者机构：Institute of Stem Cell ResearchThe Eye HospitalWenzhou Medical UniversityWenzhou 325027China Beijing Institute of OphthalmologyBeijing Tongren Eye CenterBeijing Tongren HospitalCapital Medical UniversityBeijing Ophthalmology&Visual Sciences Key LaboratoryBeijing 100730China 

出 版 物：《Science China(Life Sciences)》 (中国科学（生命科学英文版）)

年 卷 期：2022年第65卷第6期

页      面：1057-1071页

核心收录：

学科分类：0710[理学-生物学] 1001[医学-基础医学(可授医学、理学学位)] 100101[医学-人体解剖与组织胚胎学] 10[医学] 

基　　金：partly supported by the National Natural Science Foundation of China(82125007,81790644) Beijing Natural Science Foundation(Z20J00122) the National Key Research and Development Program of China(2017YFA0105300)。 

主　　题：microglia retinal organoid pluripotent stem cells differentiation human induced reprogramming 

摘      要：Microglia are known to play essential roles in the development,progression and treatment of diverse neurodegenerative diseases in the central nervous system,including the retina,brain and spinal cord.Recently,brain-induced microglia-like cells(iMGs)have been generated from human pluripotent stem cells(hPSCs);however,retinal microglia have yet to be developed in vitro.In this study,by mimicking in vivo microglial development,we established a simplified approach to differentiate hPSCs into high purity(90%)iMGs.The iMGs express microglia-specific markers,release cytokines upon stimulation,and are capable of phagocytizing bacteria.When co-cultured with three-dimensional human retinal organoids(hROs),iMGs migrated into the hROs,tended to differentiate into resident retinal microglia,and simultaneously induced apoptosis in some neural cells.Notably,the resident i MGs in the hROs formed sparse web-like structures beneath the photoreceptor cell layer,resembling microglia s orientation in human retina.In conclusion,we developed a simplified and efficient method to generate microglia from human pluripotent stem cells,and we report the first derivation of retinaresident microglia in vitro,providing a new source of human retinal microglia for developmental and disease studies and regenerative therapeutics.