Lehman College, 250 Bedford Park Boulevard West, Bronx, NY, 10468, USA.
Biology Doctoral Program, The Graduate School and University Center, City University of New York, 365 5th Avenue, New York, NY, 10016, USA.
Sci Rep. 2021 Oct 26;11(1):21128. doi: 10.1038/s41598-021-00542-w.
The mechanisms underlying retinal development have not been completely elucidated. Extracellular vesicles (EVs) are novel essential mediators of cell-to-cell communication with emerging roles in developmental processes. Nevertheless, the identification of EVs in human retinal tissue, characterization of their cargo, and analysis of their potential role in retina development has not been accomplished. Three-dimensional retinal tissue derived from human induced pluripotent stem cells (hiPSC) provide an ideal developmental system to achieve this goal. Here we report that hiPSC-derived retinal organoids release exosomes and microvesicles with small noncoding RNA cargo. EV miRNA cargo-predicted targetome correlates with Gene Ontology (GO) pathways involved in mechanisms of retinogenesis relevant to specific developmental stages corresponding to hallmarks of native human retina development. Furthermore, uptake of EVs by human retinal progenitor cells leads to changes in gene expression correlated with EV miRNA cargo predicted gene targets, and mechanisms involved in retinal development, ganglion cell and photoreceptor differentiation and function.
视网膜发育的机制尚未完全阐明。细胞外囊泡（EVs）是细胞间通讯的新型重要介质，在发育过程中发挥着新兴作用。然而，尚未在人视网膜组织中鉴定 EVs，表征其货物，并分析它们在视网膜发育中的潜在作用。源自人诱导多能干细胞（hiPSC）的三维视网膜组织为实现这一目标提供了一个理想的发育系统。在这里，我们报告 hiPSC 衍生的视网膜类器官释放含有小非编码 RNA 货物的外泌体和微泡。EV miRNA 货物预测的靶标与与特定发育阶段相关的视网膜发生机制的基因本体论（GO）途径相关，这些途径对应于天然人视网膜发育的特征。此外，人视网膜祖细胞摄取 EV 会导致与 EV miRNA 货物预测基因靶标以及涉及视网膜发育、神经节细胞和光感受器分化和功能的机制相关的基因表达发生变化。
