Brn2 Alone Is Sufficient to Convert Astrocytes into Neural Progenitors and Neurons

Stem Cells Dev. 2018 Jun 1;27(11):736-744. doi: 10.1089/scd.2017.0250. Epub 2018 May 15.

Abstract

Generating neurons or neural progenitor cells (NPCs) from astrocytes is a potential strategy for neurological repair by reprogramming. Previous study has showed that Brn2, by cooperating with other factors, participates in neurogenesis and neuronal reprogramming. However, it is still unclear whether the Brn2 alone can convert astrocytes into neurons or NPCs. Here, we explored the effect of Brn2 on reprogramming of astrocytes, and found that a single transcription factor Brn2 can convert mouse astrocytes into functional neurons. Furthermore, the Brn2-infected astrocytes can be induced into NPCs after changing culture condition. In addition, our study found that the reprogramming of astrocytes and the fate of transdifferentiated cells are closely associated with cell microenvironmental factors, such as the brain regions where the astrocytes come from, the proliferation ability of astrocytes, and culture condition of infected astrocytes. To sum up, for the first time, our results demonstrated that Brn2 alone is sufficient to convert astrocytes into neural progenitors and neurons, and the conversion is associated with cell microenvironments. This new conversion method will be a potential therapeutic approach to restore the injured diseased brain in regenerative medicine.

Keywords: Brn2; astrocytes; neural progenitors; regenerative medicine; reprogram.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / metabolism*
  • Astrocytes / physiology
  • Brain / cytology
  • Brain / metabolism
  • Cell Differentiation / genetics
  • Cell Transdifferentiation / genetics
  • Cells, Cultured
  • Cellular Reprogramming / genetics
  • Culture Media / chemistry
  • Culture Media / pharmacology
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neural Stem Cells / metabolism*
  • Neural Stem Cells / physiology
  • Neurogenesis / genetics
  • Neurons / cytology
  • Neurons / metabolism*
  • Neurons / physiology
  • POU Domain Factors / genetics
  • POU Domain Factors / metabolism*
  • Patch-Clamp Techniques

Substances

  • Culture Media
  • Nerve Tissue Proteins
  • POU Domain Factors
  • Pou3f2 protein, mouse