MicroRNAs miR-25, let-7 and miR-124 regulate the neurogenic potential of Müller glia in mice

Development. 2019 Sep 2;146(17):dev179556. doi: 10.1242/dev.179556.


Müller glial cells (MG) generate retinal progenitor (RPC)-like cells after injury in non-mammalian species, although this does not occur in the mammalian retina. Studies have profiled gene expression in these cells to define genes that may be relevant to their differences in neurogenic potential. However, less is known about differences in micro-RNA (miRNA) expression. In this study, we compared miRNAs from RPCs and MG to identify miRNAs more highly expressed in RPCs, and others more highly expressed in MG. To determine whether these miRNAs are relevant to the difference in neurogenic potential between these two cell types, we tested them in dissociated cultures of MG using either mimics or antagomiRs to increase or reduce expression, respectively. Among the miRNAs tested, miR-25 and miR-124 overexpression, or let-7 antagonism, induced Ascl1 expression and conversion of ∼40% of mature MG into a neuronal/RPC phenotype. Our results suggest that the differences in miRNA expression between MG and RPCs contribute to their difference in neurogenic potential, and that manipulations in miRNAs provide a new tool with which to reprogram MG for retinal regeneration.

Keywords: Adult; Ascl1; Reprogramming; Retina; Single cell RNA-seq; miRNAs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antagomirs / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Differentiation / genetics
  • Cells, Cultured
  • Ependymoglial Cells / metabolism*
  • Female
  • Male
  • Mice
  • Mice, Transgenic
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Nerve Regeneration / physiology
  • Neurogenesis / genetics*
  • Retina / cytology
  • Retina / metabolism
  • Retinal Neurons / metabolism
  • Transfection


  • Antagomirs
  • Ascl1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • MIRN25 microRNA, mouse
  • MicroRNAs
  • Mirn124 microRNA, mouse
  • mirnlet7 microRNA, mouse