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

Author

Listed:
  • Birthe Dorgau

    (Newcastle University)

  • Joseph Collin

    (Newcastle University)

  • Agata Rozanska

    (Newcastle University)

  • Darin Zerti

    (Newcastle University
    University of L’Aquila)

  • 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)

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.

Suggested Citation

  • 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. FitzP, 2024. "Single-cell analyses reveal transient retinal progenitor cells in the ciliary margin of developing human retina," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47933-x
    DOI: 10.1038/s41467-024-47933-x
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    References listed on IDEAS

    as
    1. Atsushi Kuwahara & Chikafumi Ozone & Tokushige Nakano & Koichi Saito & Mototsugu Eiraku & Yoshiki Sasai, 2015. "Generation of a ciliary margin-like stem cell niche from self-organizing human retinal tissue," Nature Communications, Nature, vol. 6(1), pages 1-15, May.
    2. Pradeep Gautam & Kiyofumi Hamashima & Ying Chen & Yingying Zeng & Bar Makovoz & Bhav Harshad Parikh & Hsin Yee Lee & Katherine Anne Lau & Xinyi Su & Raymond C. B. Wong & Woon-Khiong Chan & Hu Li & Tim, 2021. "Multi-species single-cell transcriptomic analysis of ocular compartment regulons," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    3. Nathaniel Kastan & Ksenia Gnedeva & Theresa Alisch & Aleksandra A. Petelski & David J. Huggins & Jeanne Chiaravalli & Alla Aharanov & Avraham Shakked & Eldad Tzahor & Aaron Nagiel & Neil Segil & A. J., 2021. "Small-molecule inhibition of Lats kinases may promote Yap-dependent proliferation in postmitotic mammalian tissues," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    4. Yang Sun & Lu Hu & Zhipeng Tao & Gopala K. Jarugumilli & Hannah Erb & Alka Singh & Qi Li & Jennifer L. Cotton & Patricia Greninger & Regina K. Egan & Y. Tony Ip & Cyril H. Benes & Jianwei Che & Junhao, 2022. "Pharmacological blockade of TEAD–YAP reveals its therapeutic limitation in cancer cells," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
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    6. Fuguo Wu & Jonathan E. Bard & Julien Kann & Donald Yergeau & Darshan Sapkota & Yichen Ge & Zihua Hu & Jie Wang & Tao Liu & Xiuqian Mu, 2021. "Single cell transcriptomics reveals lineage trajectory of retinal ganglion cells in wild-type and Atoh7-null retinas," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
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