Direct Conversion of Fibroblasts into Functional Astrocytes by Defined Transcription Factors

作者：Caiazzo Massimiliano^*; Giannelli Serena; Valente Pierluigi; Lignani Gabriele; Carissimo Annamaria; Sessa Alessandro; Co****nte Gaia; Bartolomeo Rosa; Massimino Luca; Ferroni Stefano; Settembre Carmine; Benfenati Fabio; Broccoli Vania

来源：Stem Cell Reports, 2015, 4(1): 25-36.

DOI：10.1016/j.stemcr.2014.12.002

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.

• 出版日期2015-1-13