Fish primary embryonic pluripotent cells assemble into retinal tissue mirroring in vivo early eye development

• Published in: eLife Vol. 10
• Main Authors: Zilova, Lucie, Weinhardt, Venera, Tavhelidse, Tinatini, Schlagheck, Christina, Thumberger, Thomas, Wittbrodt, Joachim
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 12.07.2021; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Aggregates; Animals; Blastula; Cell Differentiation; Developmental Biology; Embryonic Stem Cells - cytology; Embryonic Stem Cells - metabolism; Embryos; Extracellular matrix; Genetic factors; Genome editing; Genomes; Humans; in vitro organogenesis; medaka; Medical research; Morphogenesis; Morphology; Nakano, T; Organogenesis; Organoids; Organoids - cytology; Organoids - metabolism; Oryzias; Pluripotency; Pluripotent Stem Cells - physiology; Retina; Retina - cytology; Retina - growth & development; Retina - metabolism; Scientific equipment and supplies industry; Stem cell research; Stem cells; Stem Cells and Regenerative Medicine; Transcription factors; Zebrafish; Canada; United States; in vitro organogenesis; stem cells; medaka; retina; developmental biology; organoids; regenerative medicine; zebrafish
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.66998

Organoids derived from pluripotent stem cells promise the solution to current challenges in basic and biomedical research. Mammalian organoids are however limited by long developmental time, variable success, and lack of direct comparison to an in vivo reference. To overcome these limitations and address species-specific cellular organization, we derived organoids from rapidly developing teleosts. We demonstrate how primary embryonic pluripotent cells from medaka and zebrafish efficiently assemble into anterior neural structures, particularly retina. Within 4 days, blastula-stage cell aggregates reproducibly execute key steps of eye development: retinal specification, morphogenesis, and differentiation. The number of aggregated cells and genetic factors crucially impacted upon the concomitant morphological changes that were intriguingly reflecting the in vivo situation. High efficiency and rapid development of fish-derived organoids in combination with advanced genome editing techniques immediately allow addressing aspects of development and disease, and systematic probing of impact of the physical environment on morphogenesis and differentiation.