Human retinal organoids release extracellular vesicles that regulate gene expression in target human retinal progenitor cells

Jing Zhou, Miguel Flores-Bellver, Jianbo Pan, Alberto Benito-Martin, Cui Shi, Onyekwere Onwumere, Jason Mighty, Jiang Qian, Xiufeng Zhong, Tasmim Hogue, Baffour Amponsah-Antwi, Linda Einbond, Rajendra Gharbaran, Hao Wu, Bo Juen Chen, Zhiliang Zheng, Tatyana Tchaikovskaya, Xusheng Zhang, Hector Peinado, Maria Valeria Canto-SolerStephen Redenti

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number21128
JournalScientific reports
Volume11
Issue number1
DOIs
StatePublished - Dec 2021

ASJC Scopus subject areas

  • General

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