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Neurogenin1 effectively reprograms cultured chick retinal pigment epithelial cells to differentiate toward photoreceptors
Author(s) -
Yan RunTao,
Liang Lina,
Ma Wenxin,
Li Xiumei,
Xie Wenlian,
Wang ShuZhen
Publication year - 2009
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.22236
Subject(s) - biology , opsin , visual phototransduction , retina , microbiology and biotechnology , reprogramming , retinal , photoreceptor cell , muller glia , rhodopsin , intrinsically photosensitive retinal ganglion cells , retinal degeneration , transducin , retinitis pigmentosa , neuroscience , anatomy , stem cell , cell , genetics , retinal ganglion cell , progenitor cell , biochemistry
Photoreceptors are highly specialized sensory neurons in the retina, and their degeneration results in blindness. Replacement with developing photoreceptor cells promises to be an effective therapy, but it requires a supply of new photoreceptors, because the neural retina in human eyes lacks regeneration capability. We report efficient generation of differentiating, photoreceptor‐like neurons from chick retinal pigment epithelial (RPE) cells propagated in culture through reprogramming with neurogenin1 ( ngn1 ). In reprogrammed culture, a large number of the cells (85.0% ± 5.9%) began to differentiate toward photoreceptors. Reprogrammed cells expressed transcription factors that set in motion photoreceptor differentiation, including Crx, Nr2E3, NeuroD, and RXRγ, and phototransduction pathway components, including transducin, cGMP‐gated channel, and red opsin of cone photoreceptors (equivalent to rhodopsin of rod photoreceptors). They developed inner segments rich in mitochondria. Furthermore, they responded to light by decreasing their cellular free calcium (Ca 2+ ) levels and responded to 9‐cis‐retinal by increasing their Ca 2+ levels after photobleaching, hallmarks of photoreceptor physiology. The high efficiency and the advanced photoreceptor differentiation indicate ngn1 as a gene of choice to reprogram RPE progeny cells to differentiate into photoreceptor neurons in future cell replacement studies. J. Comp. Neurol. 518:526–546, 2010. © 2009 Wiley‐Liss, Inc.