Single-cell transcriptomics reveals the molecular basis of human iPS cell differentiation into ectodermal ocular lineages

Howard, Laura, Ishikawa, Yuki, Katayama, Tomohiko, Park, Sung-Joon, Hill, Matthew J. ORCID: https://orcid.org/0000-0001-6776-8709, Blake, Derek J. ORCID: https://orcid.org/0000-0002-5005-4731, Nishida, Kohji, Hayashi, Ryuhei and Quantock, Andrew J. ORCID: https://orcid.org/0000-0002-2484-3120 2024. Single-cell transcriptomics reveals the molecular basis of human iPS cell differentiation into ectodermal ocular lineages. Communications Biology 7 (1) , 1495. 10.1038/s42003-024-07130-4

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Abstract

The generation of a self-formed, ectodermal, autonomous multi-zone (SEAM) from human induced pluripotent stem cells (hiPSCs) offers a unique perspective to study the dynamics of ocular cell differentiation over time. Here, by utilising single-cell transcriptomics, we have (i) identified, (ii) molecularly characterised and (iii) ascertained the developmental trajectories of ectodermally-derived ocular cell populations which emerge within SEAMs as they form. Our analysis reveals interdependency between tissues of the early eye and delineates the sequential formation and maturation of distinct cell types over a 12-week period. We demonstrate a progression from pluripotency through to tissue specification and differentiation which encompasses both surface ectodermal and neuroectodermal ocular lineages and the generation of iPSC-derived components of the developing cornea, conjunctiva, lens, and retina. Our findings not only advance the understanding of ocular development in a stem cell-based system of human origin, but also establish a robust methodological paradigm for exploring cellular and molecular dynamics during SEAM formation at single-cell resolution and highlight the potential of hiPSC-derived systems as powerful platforms for modelling human eye development and disease.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Optometry and Vision Sciences Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/, Type: open-access
Publisher:	Nature Research
ISSN:	2399-3642
Date of Acceptance:	23 October 2024
Last Modified:	14 Nov 2024 11:45
URI:	https://orca.cardiff.ac.uk/id/eprint/174004

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