Fate-restricted retinal progenitor cells adopt a molecular profile and spatial position distinct from multipotent progenitor cells

• Published in: Developmental biology Vol. 443; no. 1; pp. 35 - 49
• Main Authors: Buenaventura, Diego F., Ghinia-Tegla, Miruna G., Emerson, Mark M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-11-2018
• Subjects: Animals; Cell Differentiation - physiology; Cell Lineage - genetics; Chick Embryo; Cone photoreceptor; Gene Expression Regulation, Developmental - genetics; Genes, erbA - genetics; Homeodomain Proteins - genetics; LIM-Homeodomain Proteins - genetics; Mice; PAX6 Transcription Factor - genetics; Restricted progenitor; Retina - cytology; Retina - embryology; Retinal Cone Photoreceptor Cells - metabolism; Retinal Cone Photoreceptor Cells - physiology; Stem Cells - physiology; Transcription Factors - genetics; Transcriptome; Transcriptome - genetics; Restricted progenitor; Transcriptome; Cone photoreceptor
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2018.06.023

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.
•Transcriptome of retinal progenitors restricted to cone and horizontal cell fates.•Progenitor cell genes are regulated differently in specific progenitor populations.•The nuclei of different progenitor populations occupy unique spatial locations.•Gene regulatory networks in restricted progenitor cells repress multipotent programs.