Plagl1 regulates the retinal progenitor cell to Müller glial cell transition
Abstract
Müller glia arise from late-stage retinal progenitor cells (RPCs) as a distinct lineage that diverges from neurogenic trajectories. Here, we identify the maternally imprinted gene Plagl1 as a key transcriptional regulator of gliogenesis in the murine retina. Plagl1 is expressed during the RPC-to-glia transition and is dynamically regulated in Müller glia following injury. To define its developmental role, we analyzed Plagl1⁺/⁻pat null mutant retinas at postnatal day 7 (P7), when central retinal gliogenesis is complete. In the absence of Plagl1, Sox9 ⁺ glial/precursor cells were displaced and proliferated ectopically, with structural dysmorphologies, reactive gliosis, and impaired visual processing persisting into later postnatal stages. Bulk RNA-seq and ATAC-seq revealed widespread reductions in chromatin accessibility and transcriptional dysregulation affecting epigenetic modifiers, translational machinery, fate-specifying transcription factors, cell cycle regulators, and signaling pathways. Single-cell pseudobulk analysis showed that Plagl1 loss disrupts chromatin, transcriptional, and translational programs specifically within Sox9 ⁺ cells, encompassing Müller glia and precursor populations, pinpointing these cells as the source of defects in Plagl1⁺/⁻pat retinas. Notch signaling was elevated in Plagl1-deficient glia, and genetic activation at P14 displaced Sox9 ⁺ glial cells, without inducing proliferation. Similarly, conditional deletion of Plagl1 in postnatal Müller glia at P14 disrupted positioning and not cell cycle exit, confirming a cell-autonomous requirement for Müller glia positioning that is independent of proliferation control. Since these conditional manipulations could only be performed at P14 at the earliest, they reveal Plagl1's later functions in postmitotic glia and complement, rather than mirror, the earlier P7 mixed RPC/glial null phenotype. Together these findings establish Plagl1 as a critical regulator of the late-stage RPC to Müller glia transition, acting through coordinated control of chromatin accessibility and gene expression programs to ensure timely cell cycle exit. This function aligns with Plagl1's broader tumor suppressor role in stabilizing postmitotic, differentiated cell states across tissues.
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BibTeX
@article{touahri2026plagl1,
title = {{Plagl1 regulates the retinal progenitor cell to Müller glial cell transition}},
author = {Yacine Touahri and Alissa Pak and Luke Ajay David and Joseph Hanna and Hedy Liu and Yucheng Xiao and Lauren Belfiore and Yaroslav Ilnytskyy and Edwin van Oosten and Nobuhiko Tachibana and Lata Adnani and Jiayi Zhao and Mary Hoffman and Rajiv Dixit and Dawn Zinyk and Cynthia Guidos and Volker Enzmann and Pengpeng Bi and Isabelle Aubert and Laurent Journot and Igor Kovalchuk and Yves Sauvé and Jeff Biernaskie and Chao Wang and Satoshi Okawa and Antonio del Sol and Carol Schuurmans},
journal = {PLoS Genetics},
year = {2026},
month = sep,
doi = {10.1371/journal.pgen.1012020},
url = {https://hal.science/hal-05764454v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Plagl1 regulates the retinal progenitor cell to Müller glial cell transition
AU - Yacine Touahri
AU - Alissa Pak
AU - Luke Ajay David
AU - Joseph Hanna
AU - Hedy Liu
AU - Yucheng Xiao
AU - Lauren Belfiore
AU - Yaroslav Ilnytskyy
AU - Edwin van Oosten
AU - Nobuhiko Tachibana
AU - Lata Adnani
AU - Jiayi Zhao
AU - Mary Hoffman
AU - Rajiv Dixit
AU - Dawn Zinyk
AU - Cynthia Guidos
AU - Volker Enzmann
AU - Pengpeng Bi
AU - Isabelle Aubert
AU - Laurent Journot
AU - Igor Kovalchuk
AU - Yves Sauvé
AU - Jeff Biernaskie
AU - Chao Wang
AU - Satoshi Okawa
AU - Antonio del Sol
AU - Carol Schuurmans
PY - 2026
DA - 2026/09/25
JO - PLoS Genetics
DO - 10.1371/journal.pgen.1012020
UR - https://hal.science/hal-05764454v1
AB - Müller glia arise from late-stage retinal progenitor cells (RPCs) as a distinct lineage that diverges from neurogenic trajectories. Here, we identify the maternally imprinted gene Plagl1 as a key transcriptional regulator of gliogenesis in the murine retina. Plagl1 is expressed during the RPC-to-glia transition and is dynamically regulated in Müller glia following injury. To define its developmental role, we analyzed Plagl1⁺/⁻pat null mutant retinas at postnatal day 7 (P7), when central retinal gliogenesis is complete. In the absence of Plagl1, Sox9 ⁺ glial/precursor cells were displaced and proliferated ectopically, with structural dysmorphologies, reactive gliosis, and impaired visual processing persisting into later postnatal stages. Bulk RNA-seq and ATAC-seq revealed widespread reductions in chromatin accessibility and transcriptional dysregulation affecting epigenetic modifiers, translational machinery, fate-specifying transcription factors, cell cycle regulators, and signaling pathways. Single-cell pseudobulk analysis showed that Plagl1 loss disrupts chromatin, transcriptional, and translational programs specifically within Sox9 ⁺ cells, encompassing Müller glia and precursor populations, pinpointing these cells as the source of defects in Plagl1⁺/⁻pat retinas. Notch signaling was elevated in Plagl1-deficient glia, and genetic activation at P14 displaced Sox9 ⁺ glial cells, without inducing proliferation. Similarly, conditional deletion of Plagl1 in postnatal Müller glia at P14 disrupted positioning and not cell cycle exit, confirming a cell-autonomous requirement for Müller glia positioning that is independent of proliferation control. Since these conditional manipulations could only be performed at P14 at the earliest, they reveal Plagl1's later functions in postmitotic glia and complement, rather than mirror, the earlier P7 mixed RPC/glial null phenotype. Together these findings establish Plagl1 as a critical regulator of the late-stage RPC to Müller glia transition, acting through coordinated control of chromatin accessibility and gene expression programs to ensure timely cell cycle exit. This function aligns with Plagl1's broader tumor suppressor role in stabilizing postmitotic, differentiated cell states across tissues.
SN - 1553-7390
SN - 1553-7404
ER -