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

Stem Cell Research

Kenneth N. Grisé^1¹  Saeed Khalili^1²  Brian G. Ballios^2,1³  Justin Belair-Hickey^1⁴  Laura Donaldson^3⁵  Brenda L.K. Coles^1⁶  Tahani Baakdhah^8⁷  Jeff Liu^1⁸ 

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

关键词: Stem cell;    Retina;    Rod photoreceptor;    Cone photoreceptor;    Progenitors;   

DOI  :  10.1016/j.scr.2018.11.005

学科分类：生物科学（综合）

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Unknown