Repository logo
 

Retinal Organoids from Pluripotent Stem Cells Efficiently Recapitulate Retinogenesis.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Zschätzsch, Marlen 
Rostovskaya, Maria 

Abstract

The plasticity of pluripotent stem cells provides new possibilities for studying development, degeneration, and regeneration. Protocols for the differentiation of retinal organoids from embryonic stem cells have been developed, which either recapitulate complete eyecup morphogenesis or maximize photoreceptor genesis. Here, we have developed a protocol for the efficient generation of large, 3D-stratified retinal organoids that does not require evagination of optic-vesicle-like structures, which so far limited the organoid yield. Analysis of gene expression in individual organoids, cell birthdating, and interorganoid variation indicate efficient, reproducible, and temporally regulated retinogenesis. Comparative analysis of a transgenic reporter for PAX6, a master regulator of retinogenesis, shows expression in similar cell types in mouse in vivo, and in mouse and human retinal organoids. Early or late Notch signaling inhibition forces cell differentiation, generating organoids enriched with cone or rod photoreceptors, respectively, demonstrating the power of our improved organoid system for future research in stem cell biology and regenerative medicine.

Description

Keywords

Animals, Cell Differentiation, Cells, Cultured, Gene Expression Profiling, Human Embryonic Stem Cells, Humans, Mice, Mice, Transgenic, Microscopy, Confocal, Mouse Embryonic Stem Cells, Organ Culture Techniques, Organogenesis, Organoids, PAX6 Transcription Factor, Pluripotent Stem Cells, Retina, Reverse Transcriptase Polymerase Chain Reaction

Journal Title

Stem Cell Reports

Conference Name

Journal ISSN

2213-6711
2213-6711

Volume Title

6

Publisher

Elsevier BV