RT Journal Article
SR Electronic
T1 Dual SMAD inhibition and Wnt inhibition enhances the differentiation of induced pluripotent stem cells into Retinal Ganglion cells (iPSC-RGCs)
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 682666
DO 10.1101/682666
A1 Venkata R. M. Chavali
A1 Naqi Haider
A1 Sonika Rathi
A1 Teja Alapati
A1 Jie He
A1 Kamaljot Gill
A1 Sergei Nikonov
A1 Roman Nikonov
A1 Thu T. Duong
A1 Devin S. McDougald
A1 Joan O’ Brien
A1 Jason A. Mills
YR 2019
UL http://biorxiv.org/content/early/2019/07/01/682666.abstract
AB 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 death of retinal ganglion cells (RGCs). The loss of RGCs manifests as characteristic cupping or optic nerve degeneration, resulting in peripheral vision loss in patients with Glaucoma. Several initial studies carried out RGC differentiation from induced pluripotent stem cells (iPSCs) or embryonic stem cells (ESCs), by modulating classical RGC signaling pathways to mimic in vivo retinal development. Recent studies used small molecules and peptide modulators at specific intervals to fine tune RGC differentiation, and also increase the yields to produce purified RGCs. In this study, we present a chemically defined and functionally novel in vitro methodology for cultivating unprecedented yields of RPC populations from iPSCs, that are then directed toward the RGC lineage. Using this method, we differentiated control iPSC lines into RGCs using in in a stepwise manner using small molecules and peptide modulator treatment to inhibit BMP and TGF-β (SMAD), and canonical Wnt pathways yielding a robust population of iPSC-RGCs.