TY  - JOUR
AU  - Völkner, Manuela
AU  - Zschätzsch, Marlen
AU  - Rostovskaya, Maria
AU  - Overall, Rupert W
AU  - Busskamp, Volker
AU  - Anastassiadis, Konstantinos
AU  - Karl, Mike O
TI  - Retinal Organoids from Pluripotent Stem Cells Efficiently Recapitulate Retinogenesis.
JO  - Stem cell reports
VL  - 6
IS  - 4
SN  - 2213-6711
CY  - [New York, NY]
PB  - Elsevier
M1  - DZNE-2020-04811
SP  - 525-538
PY  - 2016
AB  - 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.
KW  - Animals
KW  - Cell Differentiation: genetics
KW  - Cells, Cultured
KW  - Gene Expression Profiling
KW  - Human Embryonic Stem Cells: cytology
KW  - Human Embryonic Stem Cells: metabolism
KW  - Humans
KW  - Mice
KW  - Mice, Transgenic
KW  - Microscopy, Confocal
KW  - Mouse Embryonic Stem Cells: cytology
KW  - Mouse Embryonic Stem Cells: metabolism
KW  - Organ Culture Techniques
KW  - Organogenesis: genetics
KW  - Organoids: cytology
KW  - Organoids: metabolism
KW  - PAX6 Transcription Factor: genetics
KW  - PAX6 Transcription Factor: metabolism
KW  - Pluripotent Stem Cells: cytology
KW  - Pluripotent Stem Cells: metabolism
KW  - Retina: cytology
KW  - Retina: growth & development
KW  - Retina: metabolism
KW  - Reverse Transcriptase Polymerase Chain Reaction
KW  - PAX6 Transcription Factor (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:27050948
C2  - pmc:PMC4834051
DO  - DOI:10.1016/j.stemcr.2016.03.001
UR  - https://pub.dzne.de/record/138489
ER  -