Direct conversion of fibroblasts into functional astrocytes by defined transcription factors

Massimiliano Caiazzo, Serena Giannelli, Pierluigi Valente, Gabriele Lignani, Annamaria Carissimo, Alessandro Sessa, Gaia Colasante, Rosa Bartolomeo, Luca Massimino, Stefano Ferroni, Carmine Settembre, Fabio Benfenati, Vania Broccoli

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)25-36
Number of pages12
JournalStem Cell Reports
Volume4
Issue number1
DOIs
Publication statusPublished - Jan 13 2015

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Developmental Biology
  • Genetics

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  • Cite this

    Caiazzo, M., Giannelli, S., Valente, P., Lignani, G., Carissimo, A., Sessa, A., Colasante, G., Bartolomeo, R., Massimino, L., Ferroni, S., Settembre, C., Benfenati, F., & Broccoli, V. (2015). Direct conversion of fibroblasts into functional astrocytes by defined transcription factors. Stem Cell Reports, 4(1), 25-36. https://doi.org/10.1016/j.stemcr.2014.12.002