Defined Conditions for Differentiation of Functional Retinal Ganglion Cells From Human Pluripotent Stem Cells

Investigative Ophthalmology & Visual Science
Junwon LeeDong-Wook Kim

Abstract

We aimed to establish an efficient method for retinal ganglion cell (RGC) differentiation from human pluripotent stem cells (hPSCs) using defined factors. To define the contribution of specific signal pathways to RGC development and optimize the differentiation of hPSCs toward RGCs, we examined RGC differentiation in three stages: (1) eye field progenitors expressing the eye field transcription factors (EFTFs), (2) RGC progenitors expressing MATH5, and (3) RGCs expressing BRN3B and ISLET1. By monitoring the condition that elicited the highest yield of cells expressing stage-specific markers, we determined the optimal concentrations and combinations of signaling pathways required for efficient generation of RGCs from hPSCs. Precise modulation of signaling pathways, including Wnt, insulin growth factor-1, and fibroblast growth factor, in combination with mechanical isolation of neural rosette cell clusters significantly enriched RX and PAX6 double-positive eye field progenitors from hPSCs by day 12. Furthermore, Notch signal inhibition facilitated differentiation into MATH5-positive progenitors at 90% efficiency by day 20, and these cells further differentiated to BRN3B and ISLET1 double-positive RGCs at 45% efficiency by day 40....Continue Reading

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Citations

Feb 28, 2020·Investigative Ophthalmology & Visual Science·Xiaohe YanUNKNOWN German Mouse Clinic Consortium
Oct 28, 2020·International Journal of Molecular Sciences·Ayaka EdoMasayo Takahashi
Jan 23, 2021·Genes·Marta García-LópezM Esther Gallardo
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Sep 30, 2021·Nature Communications·Pradeep GautamYuin-Han Loh

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