Plagl1 regulates the retinal progenitor cell to Müller glial cell transition - PubMed
5 hours ago
- #retinal development
- #Plagl1
- #Müller glia
- Plagl1 is identified as a key transcriptional regulator of gliogenesis in the murine retina.
- Plagl1 is expressed during the retinal progenitor cell (RPC)-to-glia transition and is dynamically regulated in Müller glia following injury.
- Plagl1 loss leads to displaced and ectopically proliferating Sox9+ glial/precursor cells, causing structural dysmorphologies, reactive gliosis, and impaired visual processing.
- Bulk RNA-seq and ATAC-seq analyses show widespread reductions in chromatin accessibility and transcriptional dysregulation in Plagl1-deficient retinas.
- Single-cell pseudobulk analysis reveals that Plagl1 loss disrupts chromatin, transcriptional, and translational programs specifically in Sox9+ cells.
- Notch signaling is elevated in Plagl1-deficient glia, and genetic activation displaces Sox9+ glial cells without inducing proliferation.
- Conditional deletion of Plagl1 in postnatal Müller glia disrupts positioning but not cell cycle exit, indicating a cell-autonomous role in positioning.
- Plagl1 functions as a critical regulator of the RPC-to-Müller glia transition by controlling chromatin accessibility and gene expression programs.
- Plagl1's role aligns with its broader tumor suppressor function in stabilizing postmitotic, differentiated cell states across tissues.