{
  "id": 8021696,
  "title": "Synergistic inhibition of Notch signaling and forced cell cycle re-entry drive Müller glia reprogramming in uninjured mouse retina",
  "url": "https://urgent.news/2026/09/17/synergistic-inhibition-of-notch-signaling-and-forced-cell-cycle-re",
  "topic": "health",
  "section": "Health & Medicine",
  "published": "2026-09-17T00:00:00.000Z",
  "source": {
    "name": "eLife",
    "slug": "elife",
    "url": "https://elifesciences.org/articles/111251"
  },
  "original_language": "en",
  "account": "Regenerative organisms, like teleost fish, possess the ability for Müller glia (MG) cells to enter the cell cycle independently following injury and generate functional retinal neurons. However, mammalian MG cells exhibit limited proliferative and regenerative abilities, resulting in irreversible loss of retinal neurons. Various methods have been employed to stimulate proliferation in adult mouse MG, yet most resulting daughter cells retain their glial identity.\n\nThe study found that MG daughter cells consistently maintained high Notch signaling, which could limit their neurogenic potential. Deleting Rbpj, the central transcriptional factor of Notch, triggered limited conversion of MG into neurons without any proliferation. Nonetheless, deleting Rbpj in conjunction with the forced proliferation of MG cells through increased expression of Ccnd1 and suppression of Cdkn1b led to significant enhancement of MG dedifferentiation and the expression of neuronal marker Otx2 in MG offspring cells within uninjured mouse retinas.\n\nBy combining Notch inhibition with MG cell cycle reactivation, the researchers observed an increase in the production of bipolar and amacrine-like cells derived from MG. Moreover, this approach promoted differentiation into ON-cone, OFF-cone, and rod-bipolar subtypes. Single-nucleus RNA and ATAC sequencing indicated that Notch inhibition facilitated the formation of MG-derived progenitor-like cells, while MG proliferation increased chromatin accessibility of neurogenic genes.\n\nInterestingly, most MG-derived cells persisted long-term with incomplete maturation. Overall, these findings elucidate the roles of Notch inhibition and MG proliferation, singly or in combination, in modulating the regenerative capacity of MG cells in the mammalian retina.",
  "summary": "In regenerative species, such as teleost fish, Müller glia (MG) autonomously re-enter the cell cycle after injury and give rise to functional retinal neurons. In contrast, the loss of retinal neurons in mammals is irreversible due to the limited proliferative and regenerative ability of MG. Various strategies have been developed to induce proliferation of mature mouse MG with or without injury,…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}