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

Authors

Jing Zhou, CUNY Lehman College
Miguel Flores‑Bellver, University of Colorado
Jianbo Pan, Johns Hopkins University
Alberto Benito‑Martin, Weill Cornell Medical College
Cui Shi, CUNY Lehman CollegeFollow
Onyekwere Onwumere, CUNY Lehman College
Jason Mighty, CUNY Lehman CollegeFollow
Jiang Qian, Johns Hopkins University
Xiufeng Zhong, Sun Yat-Sen University
Tasmim Hogue, CUNY Lehman College
Baffour Amponsah‑Antwi, CUNY Lehman College
Linda Einbond, CUNY Lehman College
Rajendra Gharbaran, CUNY Bronx Community CollegeFollow
Hao Wu, CUNY Lehman College
Bo‑Juen Chen, New York Genome Center
Zhiliang Zheng, CUNY Lehman CollegeFollow
Tatyana Tchaikovskaya, Albert Einstein College of Medicine
Xusheng Zhang, Albert Einstein College of Medicine
Hector Peinado, Spanish National Cancer Research Centre
Maria Valeria Canto‑Soler, University of Colorado
Stephen Redenti, CUNY Lehman CollegeFollow

Document Type

Article

Publication Date

2021

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.

Comments

This article was originally published in Scientific Reports, available at https://doi.org/10.1038/s41598-021-00542-w

This work is distributed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).