Single-cell analyses reveal transient retinal progenitor cells in the ciliary margin of developing human retina

Birthe Dorgau, Joseph Collin, Agata Rozanska, Darin Zerti, Adrienne Unsworth, Moira Crosier, Rafiqul Hussain, Jonathan Coxhead, Tamil Dhanaseelan, Aara Patel, Jane C. Sowden, David R. FitzPatrick, Rachel Queen () and Majlinda Lako ()
Additional contact information
Birthe Dorgau: Newcastle University
Joseph Collin: Newcastle University
Agata Rozanska: Newcastle University
Darin Zerti: Newcastle University
Adrienne Unsworth: Newcastle University
Moira Crosier: Newcastle University
Rafiqul Hussain: Newcastle University
Jonathan Coxhead: Newcastle University
Tamil Dhanaseelan: Newcastle University
Aara Patel: University College London
Jane C. Sowden: University College London
David R. FitzPatrick: University of Edinburgh
Rachel Queen: Newcastle University
Majlinda Lako: Newcastle University

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract The emergence of retinal progenitor cells and differentiation to various retinal cell types represent fundamental processes during retinal development. Herein, we provide a comprehensive single cell characterisation of transcriptional and chromatin accessibility changes that underline retinal progenitor cell specification and differentiation over the course of human retinal development up to midgestation. Our lineage trajectory data demonstrate the presence of early retinal progenitors, which transit to late, and further to transient neurogenic progenitors, that give rise to all the retinal neurons. Combining single cell RNA-Seq with spatial transcriptomics of early eye samples, we demonstrate the transient presence of early retinal progenitors in the ciliary margin zone with decreasing occurrence from 8 post-conception week of human development. In retinal progenitor cells, we identified a significant enrichment for transcriptional enhanced associate domain transcription factor binding motifs, which when inhibited led to loss of cycling progenitors and retinal identity in pluripotent stem cell derived organoids.

Date: 2024
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DOI: 10.1038/s41467-024-47933-x

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