Chemical induction of neurogenic properties in mammalian Müller glia

Xiaohuan Xia, Pooja Teotia, Hiren Patel, Matthew J. Van Hook, Iqbal Ahmad

Research output: Contribution to journalArticlepeer-review

Abstract

Müller glia (MG), cells that maintain homeostasis in the retina, are dormant stem cells that can regenerate neurons upon injury. However, the regenerative property of MG, which is reproducibly displayed in the lower vertebrates, is not readily observed in the mammals even upon forced expression of regulatory genes or exposure to growth factors. Here, we demonstrate a reproducible unmasking of the neurogenic properties of enriched rodent MG by serial exposure to different combinations of small molecules. The enriched MG, in response to changing culture conditions, silenced glia-specific genes and acquired transcriptional signature of neurons, accompanied by upregulation of genes known to regulate neuronal potential of MG. The MG-derived neurons expressed immunoreactivities corresponding to neuronal proteins and displayed electrophysiological features of immature neurons. Our study presents a proof of principle of pharmacological activation of neurogenic properties of mammalian MG, which may be utilized for therapeutic regeneration.

Original languageEnglish (US)
JournalSTEM CELLS
DOIs
StateAccepted/In press - 2021

Keywords

  • Müller glia
  • RNA-seq
  • chemical reprogramming
  • neurogenesis
  • small molecules

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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