Generation of neural stem cells from adult astrocytes by using a single reprogramming factor

J Cell Physiol. 2019 Aug;234(10):18697-18706. doi: 10.1002/jcp.28510. Epub 2019 Mar 25.

Abstract

Generating neural stem cells (NSCs) from astroglia as an abundant cell type in the mammalian brain has a promising outlook to be used in cell-replacement therapy for treatment of neurodegenerative disorders and neuronal trauma. However, little is known about a single reprogramming factor that may lead to the generation of induced NSCs (iNSCs) from adult brain-derived astrocytes in the absence of extrinsic inductive signals. Here, we show that zinc-finger nuclear protein Zfp521 alone is sufficient for converting the adult mouse brain-derived astrocytes into iNSCs. In vitro, Zfp521-iNSCs demonstrated long-term self-renewal and multipotency and expressed related markers. Moreover, single-seeded iNSCs were able to produce NSC colonies. These results suggest that application of Zfp521 to generate iNSCs could be regarded as a new approach for conversion of resident astrocytes into iNSCs in cell therapy for in vivo treatment of neural injuries.

Keywords: Zfp521; adult astrocyte; conversion; neural stem cells; reprogramming.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Animals
  • Astrocytes / cytology*
  • Astrocytes / metabolism*
  • Cell Differentiation*
  • Cellular Reprogramming*
  • Clone Cells
  • Mice
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism
  • Neurons / cytology
  • Neurons / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Evi3 protein, mouse
  • Transcription Factors