NEUROD1 Instructs Neuronal Conversion in Non-Reactive Astrocytes

Stem Cell Reports. 2017 Jun 6;8(6):1506-1515. doi: 10.1016/j.stemcr.2017.04.013. Epub 2017 May 11.


Currently, all methods for converting non-neuronal cells into neurons involve injury to the brain; however, whether neuronal transdifferentiation can occur long after the period of insult remains largely unknown. Here, we use the transcription factor NEUROD1, previously shown to convert reactive glial cells to neurons in the cortex, to determine whether astrocyte-to-neuron transdifferentiation can occur under physiological conditions. We utilized adeno-associated virus 9 (AAV9), which crosses the blood-brain barrier without injury, to deliver NEUROD1 to astrocytes through an intravascular route. Interestingly, we found that a small, but significant number of non-reactive astrocytes converted to neurons in the striatum, but not the cortex. Moreover, astrocytes cultured to minimize their proliferative potential also exhibited limited neuronal transdifferentiation with NEUROD1 expression. Our results show that a single transcription factor can induce astrocyte-to-neuron conversion under physiological conditions, potentially facilitating future clinical approaches long after the acute injury phase.

Keywords: AAV9; NeuroD; astrocytes; cortex; neurons; reprogramming; striatum; transdifferentiation.

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / metabolism*
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Blood-Brain Barrier / metabolism
  • Cell Differentiation
  • Cell Transdifferentiation
  • Cells, Cultured
  • Cellular Reprogramming
  • Corpus Striatum / metabolism
  • Dependovirus / genetics
  • Genetic Vectors / genetics
  • Genetic Vectors / metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / cytology
  • Neurons / metabolism*
  • Rats


  • Basic Helix-Loop-Helix Transcription Factors
  • Nerve Tissue Proteins
  • Neurogenic differentiation factor 1