Dual SMAD inhibition and Wnt inhibition enable efficient and reproducible differentiations of induced pluripotent stem cells into retinal ganglion cells.

Scientific Reports
Venkata R.M. ChavaliJason A Mills

Abstract

Glaucoma is a group of progressive optic neuropathies that share common biological and clinical characteristics including irreversible changes to the optic nerve and visual field loss caused by the death of retinal ganglion cells (RGCs). The loss of RGCs manifests as characteristic cupping or optic nerve degeneration, resulting in visual field loss in patients with Glaucoma. Published studies on in vitro RGC differentiation from stem cells utilized classical RGC signaling pathways mimicking retinal development in vivo. Although many strategies allowed for the generation of RGCs, increased variability between experiments and lower yield hampered the cross comparison between individual lines and between experiments. To address this critical need, we developed a reproducible chemically defined in vitro methodology for generating retinal progenitor cell (RPC) populations from iPSCs, that are efficiently directed towards RGC lineage. Using this method, we reproducibly differentiated iPSCs into RGCs with greater than 80% purity, without any genetic modifications. We used small molecules and peptide modulators to inhibit BMP, TGF-β (SMAD), and canonical Wnt pathways that reduced variability between iPSC lines and yielded functional an...Continue Reading

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Citations

Nov 17, 2020·Frontiers in Cell and Developmental Biology·Oriane RabesandratanaGael Orieux
Jan 23, 2021·Genes·Marta García-LópezM Esther Gallardo
May 1, 2021·Progress in Retinal and Eye Research·K EastlakeG A Limb
Aug 28, 2021·Biology·Philip Jalink, Massimiliano Caiazzo

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Methods Mentioned

BETA
FACS
flow cytometry
PCR
activated cell sorting

Software Mentioned

FlowJo
Clampex
Prism
TreeStar

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