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-Soler; Stephen Redenti

doi:10.1038/s41598-021-00542-w

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

Sci Rep. 2021 Oct 26;11(1):21128. doi: 10.1038/s41598-021-00542-w.

Authors

Jing Zhou^#^{1

2}, Miguel Flores-Bellver^#³, Jianbo Pan⁴, Alberto Benito-Martin⁵, Cui Shi¹, Onyekwere Onwumere¹, Jason Mighty^{1

2}, Jiang Qian⁴, Xiufeng Zhong⁶, Tasmim Hogue¹, Baffour Amponsah-Antwi¹, Linda Einbond¹, Rajendra Gharbaran⁷, Hao Wu^{1

2}, Bo-Juen Chen⁸, Zhiliang Zheng¹, Tatyana Tchaikovskaya⁹, Xusheng Zhang¹⁰, Hector Peinado¹¹, Maria Valeria Canto-Soler¹², Stephen Redenti^{13

14

15}

Affiliations

¹ Lehman College, 250 Bedford Park Boulevard West, Bronx, NY, 10468, USA.
² Biology Doctoral Program, The Graduate School and University Center, City University of New York, 365 5th Avenue, New York, NY, 10016, USA.
³ CellSight Ocular Stem Cell and Regeneration Program, Department of Ophthalmology, Sue Anschutz- Rodgers Eye Center, University of Colorado, 12800 East 19th Avenue, Aurora, CO, 80045, USA.
⁴ Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
⁵ Departments of Pediatrics, Hematology/Oncology Division, Weill Medical College of Cornell University, 413 E. 69th St., New York, NY, 10021, USA.
⁶ State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, Guangdong, China.
⁷ Bronx Community College, 2155 University Ave, Bronx, NY, 10453, USA.
⁸ New York Genome Center, New York, NY, 10013, USA.
⁹ Department of Medicine, Liver Research Center, Albert Einstein College of Medicine, Bronx, NY, USA.
¹⁰ Department of Medicine, Computational Genomics Core in Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA.
¹¹ Microenvironment and Metastasis Laboratory, Department of Molecular Oncology, Spanish National Cancer Research Centre (CNIO), 28029, Madrid, Spain.
¹² CellSight Ocular Stem Cell and Regeneration Program, Department of Ophthalmology, Sue Anschutz- Rodgers Eye Center, University of Colorado, 12800 East 19th Avenue, Aurora, CO, 80045, USA. [email protected].
¹³ Lehman College, 250 Bedford Park Boulevard West, Bronx, NY, 10468, USA. [email protected].
¹⁴ Biology Doctoral Program, The Graduate School and University Center, City University of New York, 365 5th Avenue, New York, NY, 10016, USA. [email protected].
¹⁵ Biochemistry Doctoral Program, The Graduate School, City University of New York, 365 Fifth Avenue, New York, NY, 10016, USA. [email protected].

^# Contributed equally.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cell Communication*
Extracellular Vesicles / metabolism*
Gene Expression Regulation*
Humans
Induced Pluripotent Stem Cells / cytology
Induced Pluripotent Stem Cells / metabolism*
Organoids / cytology
Organoids / metabolism*
Retina / cytology
Retina / metabolism*

Abstract

Publication types

MeSH terms

Grants and funding