SWI/SNF complexes are required for retinal pigmented epithelium differentiation and for the inhibition of cell proliferation and neural differentiation programs

Shai Ovadia, Guizhong Cui, Ran Elkon, Mazal Cohen-Gulkar, Nitay Zuk-Bar, Tran Tuoc, Naihe Jing*, Ruth Ashery-Padan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

During embryonic development, tissue-specific transcription factors and chromatin remodelers function together to ensure gradual, coordinated differentiation of multiple lineages. Here, we define this regulatory interplay in the developing retinal pigmented epithelium (RPE), a neuroectodermal lineage essential for the development, function and maintenance of the adjacent retina. We present a highresolution spatial transcriptomic atlas of the developing mouse RPE and the adjacent ocular mesenchyme obtained by geographical position sequencing (Geo-seq) of a single developmental stage of the eye that encompasses young and more mature ocular progenitors. These transcriptomic data, available online, reveal the key transcription factors and their gene regulatory networks during RPE and ocular mesenchyme differentiation. Moreover, conditional inactivation followed by Geo-seq revealed that this differentiation program is dependent on the activity of SWI/SNF complexes, shown here to control the expression and activity of RPE transcription factors and, at the same time, inhibit neural progenitor and cell proliferation genes. The findings reveal the roles of the SWI/SNF complexes in controlling the intersection between RPE and neural cell fates and the coupling of cell-cycle exit and differentiation.

Original languageEnglish
Article numberdev201488
JournalDevelopment (Cambridge)
Volume150
Issue number16
DOIs
StatePublished - Aug 2023

Funding

FundersFunder number
Amédée Maratier Institute for the Study of Blindness
European Union European Cooperation in Science and Technology
Sagol Center for Regenerative Medicine, Tel Aviv University
Yoran Institute
Yoran Institute for Human Genome Research
Zimin Institute
European Cooperation in Science and Technology317652, CA-18116
Israel Science Foundation1128/20
Tel Aviv University
Ministry of Science and Technology, Israel3-17557
Ministry of Health, State of Israel

    Keywords

    • Eye development
    • Gene regulatory networks
    • Mouse
    • RPE
    • SWI/SNF

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