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Initiating Differentiation in Immortalized Multipotent Otic Progenitor Cells
Published on: January 2, 2016
Fate-restricted retinal progenitor cells adopt a molecular profile and spatial position distinct from multipotent
Diego F Buenaventura1, Miruna G Ghinia-Tegla2, Mark M Emerson1
1Department of Biology, The City College of New York, City University of New York, New York, NY 10031, United States; Biology Ph.D. Program, Graduate Center, City University of New York, New York, NY 10031, United States.
Abstract:
During development, multipotent retinal progenitor cells generate a large number of unique cell types. Recent evidence suggests that there are fate-restricted progenitor cell states in addition to multipotent ones. Here we report a transcriptomic analysis of fate- restricted progenitor cells biased to produce cone photoreceptors and horizontal cells, marked by the THRB cis-regulatory element ThrbCRM1. Comparison to a control population enriched in multipotent progenitor cells identified several genes considered to be pan-progenitor, such as VSX2, LHX2, and PAX6, as downregulated in these fate- restricted retinal progenitor cells. This differential regulation occurs in chick and in a different restricted progenitor population in mouse suggesting that this is a conserved feature of progenitor dynamics during retinal development. S-phase labeling also revealed that nuclear positions of restricted progenitor populations occupy distinct spatial niches within the developing chick retina. Using a conserved regulatory element proximal to the VSX2 gene, a potential negative feedback mechanism from specific transcription factors enriched in cone/horizontal cell progenitor cells was identified. This study identifies conserved molecular and cellular changes that occur during the generation of fate restricted retinal progenitor cells from multipotent retinal progenitor cells.
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