CRX expression in pluripotent stem cell derived photoreceptors marks a transplantable subpopulation of early cones

In this study we investigated the transcriptional profile of CRX‐expressing photoreceptor precursors derived from human pluripotent stem cells and their engraftment capacity in an animal model of retinitis pigmentosa (Pde6brd1), which is characterised by rapid photoreceptor degeneration. Single cell RNA ‐Seq analysis revealed the presence of a dominant cell cluster comprising 72% of the cells, which displayed the hallmarks of early cone photoreceptor expression. When transplanted subretinally into thePde6brd1 mice, the CRX+ cells settled next to the inner nuclear layer, made connections with the inner neurons of the host retina and approximately one third expressed the pan cone marker, Arrestin 3, indicating further maturation upon integration into the host retina. Together our data provide valuable molecular insights into the transcriptional profile of human pluripotent stem cells derived CRX+ photoreceptor precursors and indicate their usefulness as a source of transplantable cone photoreceptors.Significance statementDiseases affecting the retina, the light sensitive extension of the central nervous system, account for approximately 26% of global blindness. Human pluripotent stem cells have been shown to differentiate into various retinal cell types, including photoreceptors, which can be enriched by cell surface or fluorescent molecule tagging approaches. We have investigated the molecular heterogeneity of photoreceptor precursors derived from human pluripotent stem ce...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research