Direct Conversion of Fibroblasts into Functional Astrocytes by Defined Transcription Factors

• DOI: 10.1016/j.stemcr.2014.12.002
• Publication Date: 2014-12-31T18:31:59Z
• Authors: 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
• Keywords: molecular cloning; Medicine (General); nervous system development; cell migration; Gene Expression; animal cell; fibroblast; nerve cell differentiation; Membrane Potentials; transcription factor Sox9; Mice; virus infection; Cluster Analysis; Biology (General); transcription factor; Cells, Cultured; 0303 health sciences; disease course; oligodendroglia; article; nuclear factor I; Cellular Reprogramming; unclassified drug; Phenotype; priority journal; nuclear factor 1b; Animals; Astrocytes; Biomarkers; Cell Transdifferentiation; Cells, Cultured; Cellular Reprogramming; Cluster Analysis; Cytokines; Fibroblasts; Gene Expression; Gene Expression Profiling; Humans; Membrane Potentials; Mice; Phenotype; Transcription Factors; Biochemistry; Cell Biology; Developmental Biology; Genetics; nuclear factor 1a; Cytokines; Animals; Astrocytes; Biological Markers; Cell Transdifferentiation; Cells, Cultured; Cellular Reprogramming; Cluster Analysis; Cytokines; Fibroblasts; Gene Expression; Gene Expression Profiling; Humans; Membrane Potentials; Mice; Phenotype; Transcription Factors; Biochemistry; Cell Biology; Developmental Biology; Genetics; skin fibroblast; immunoreactivity; QH301-705.5; cell stimulation; cells by body anatomy; cell selection; Article; 03 medical and health sciences; astrocyte; R5-920; SDG 3 - Good Health and Well-being; gene expression profiling; nuclear reprogramming; Animals; Humans; cell lineage; mouse; nonhuman; Gene Expression Profiling; Fibroblasts; Astrocytes; Cell Transdifferentiation; Biomarkers; Transcription Factors

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.