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CRX Expression in Pluripotent Stem Cell‐Derived Photoreceptors Marks a Transplantable Subpopulation of Early Cones

Lookup NU author(s): Dr Joseph Collin, Dr Darin Zerti, Dr Rachel Queen, Dr Roman Bauer, Dr Jonathan Coxhead, Raf Hussain, David Steel, Dr Carla Mellough, Professor Evelyne Sernagor, Professor Lyle Armstrong, Professor Majlinda Lako

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Death of photoreceptors is a common cause of age related and inherited retinal dystrophies, thus their replenishment from renewable stem cell sources is a highly desirable therapeutic goal. Human pluripotent stem cells provide a useful cell source in view of their limitless self-renewal capacity and potential to differentiate not only into cells of the retina but also self-organize into tissue with structure akin to the human retina as part of three dimensional retinal organoids. Photoreceptor precursors have been isolated from differentiating human pluripotent stem cells through application of cell surface markers or fluorescent reporter approaches and shown to have a similar transcriptome to foetal photoreceptors. 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 the Pde6brd1 mice, the CRX+ cells settled next to the inner nuclear layer, made connections with the inner neurons of the host retina and about 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.


Publication metadata

Author(s): Collin J, Zerti D, Queen R, SantoFerreira T, Bauer R, Coxhead J, Hussain R, Steel D, Mellough C, Ader M, Sernagor E, Armstrong L, Lako M

Publication type: Article

Publication status: Published

Journal: Stem Cells (Durham)

Year: 2019

Volume: 37

Issue: 5

Pages: 609-622

Print publication date: 01/05/2019

Online publication date: 25/01/2019

Acceptance date: 03/12/2018

ISSN (print): 1066-5099

ISSN (electronic): 1549-4918

Publisher: AlphaMed Press, Inc.

URL: https://doi.org/10.1002/stem.2974

DOI: 10.1002/stem.2974


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