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Stem Cell Res. 2018 Dec;33:215-227. doi: 10.1016/j.scr.2018.11.005. Epub 2018 Nov 13.

Induction of rod versus cone photoreceptor-specific progenitors from retinal precursor cells.

Author information

1
Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
2
Department of Ophthalmology and Vision Sciences, University of Toronto, 340 College Street, Suite 400, Toronto, Ontario M5T 3A9, Canada.
3
Division of Ophthalmology, Department of Surgery, Faculty of Health Sciences, McMaster University, 2757 King Street East, Hamilton, Ontario L8G 4X3, Canada.
4
Institute of Medical Science, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.
5
Department of Ophthalmology and Vision Sciences, University of Toronto, 340 College Street, Suite 400, Toronto, Ontario M5T 3A9, Canada; Donald K Johnson Eye Institute, Krembil Research Institute, University Health Network, 60 Leonard Ave., Rm 8KD413, Toronto, Ontario M5T 2S8, Canada.
6
Stem Cell and Developmental Biology Laboratory, Hôpital Maisonneuve-Rosemont, 5415 Boul. l'Assomption, Montréal H1T 2M4, Canada; Faculté de Médecine, Départment de Neurosciences, Université de Montréal, Montréal H3T 1J4, Canada.
7
Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, Ontario M5S 3E5, Canada.
8
Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada. Electronic address: derek.van.der.kooy@utoronto.ca.

Abstract

During development, multipotent progenitors undergo temporally-restricted differentiation into post-mitotic retinal cells; however, the mechanisms of progenitor division that occurs during retinogenesis remain controversial. Using clonal analyses (lineage tracing and single cell cultures), we identify rod versus cone lineage-specific progenitors derived from both adult retinal stem cells and embryonic neural retinal precursors. Taurine and retinoic acid are shown to act in an instructive and lineage-restricted manner early in the progenitor lineage hierarchy to produce rod-restricted progenitors from stem cell progeny. We also identify an instructive, but lineage-independent, mechanism for the specification of cone-restricted progenitors through the suppression of multiple differentiation signaling pathways. These data indicate that exogenous signals play critical roles in directing lineage decisions and resulting in fate-restricted rod or cone photoreceptor progenitors in culture. Additional factors may be involved in governing photoreceptor fates in vivo.

KEYWORDS:

Cone photoreceptor; Progenitors; Retina; Rod photoreceptor; Stem cell

PMID:
30453152
DOI:
10.1016/j.scr.2018.11.005
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