Direct conversion of fibroblasts into functional astrocytes by defined transcription factors

Stem Cell Reports. 2015 Jan 13;4(1):25-36. doi: 10.1016/j.stemcr.2014.12.002. Epub 2014 Dec 31.


Direct cell reprogramming enables direct conversion of fibroblasts into functional neurons and oligodendrocytes using a minimal set of cell-lineage-specific transcription factors. This approach is rapid and simple, generating the cell types of interest in one step. However, it remains unknown whether this technology can be applied to convert fibroblasts into astrocytes, the third neural lineage. Astrocytes play crucial roles in neuronal homeostasis, and their dysfunctions contribute to the origin and progression of multiple human diseases. Herein, we carried out a screening using several transcription factors involved in defining the astroglial cell fate and identified NFIA, NFIB, and SOX9 to be sufficient to convert with high efficiency embryonic and postnatal mouse fibroblasts into astrocytes (iAstrocytes). We proved both by gene-expression profiling and functional tests that iAstrocytes are comparable to native brain astrocytes. This protocol can be then employed to generate functional iAstrocytes for a wide range of experimental applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / cytology*
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Biomarkers
  • Cell Transdifferentiation / drug effects
  • Cell Transdifferentiation / genetics*
  • Cells, Cultured
  • Cellular Reprogramming / genetics
  • Cluster Analysis
  • Cytokines / metabolism
  • Cytokines / pharmacology
  • Fibroblasts / cytology*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism*
  • Gene Expression
  • Gene Expression Profiling
  • Humans
  • Membrane Potentials / drug effects
  • Membrane Potentials / genetics
  • Mice
  • Phenotype
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism


  • Biomarkers
  • Cytokines
  • Transcription Factors