TY - JOUR
T1 - Human retinal organoids release extracellular vesicles that regulate gene expression in target human retinal progenitor cells
AU - Zhou, Jing
AU - Flores-Bellver, Miguel
AU - Pan, Jianbo
AU - Benito-Martin, Alberto
AU - Shi, Cui
AU - Onwumere, Onyekwere
AU - Mighty, Jason
AU - Qian, Jiang
AU - Zhong, Xiufeng
AU - Hogue, Tasmim
AU - Amponsah-Antwi, Baffour
AU - Einbond, Linda
AU - Gharbaran, Rajendra
AU - Wu, Hao
AU - Chen, Bo Juen
AU - Zheng, Zhiliang
AU - Tchaikovskaya, Tatyana
AU - Zhang, Xusheng
AU - Peinado, Hector
AU - Canto-Soler, Maria Valeria
AU - Redenti, Stephen
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-021-00542-w
DO - 10.1038/s41598-021-00542-w
M3 - Article
C2 - 34702879
AN - SCOPUS:85118234987
SN - 2045-2322
VL - 11
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 21128
ER -