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

Direct conversion of fibroblasts into functional astrocytes by defined transcription factors.

Author information

1
Stem Cell and Neurogenesis Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan 20132, Italy. Electronic address: massimiliano.caiazzo@epfl.ch.
2
Stem Cell and Neurogenesis Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan 20132, Italy.
3
Section of Physiology, Department of Experimental Medicine, University of Genoa and National Institute of Neuroscience, 16132 Genoa, Italy.
4
Department of Neuroscience and Brain Technologies, Italian Institute of Technology, 16132 Genoa, Italy.
5
Telethon Institute of Genetics and Medicine, Naples 80131, Italy.
6
Telethon Institute of Genetics and Medicine, Naples 80131, Italy; Dulbecco Telethon Institute.
7
Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy.
8
Telethon Institute of Genetics and Medicine, Naples 80131, Italy; Dulbecco Telethon Institute; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA; Medical Genetics, Department of Medical and Translational Science Unit, Federico II University, Via Pansini 5, 80131 Naples, Italy.
9
Section of Physiology, Department of Experimental Medicine, University of Genoa and National Institute of Neuroscience, 16132 Genoa, Italy; Department of Neuroscience and Brain Technologies, Italian Institute of Technology, 16132 Genoa, Italy.
10
Stem Cell and Neurogenesis Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan 20132, Italy. Electronic address: broccoli.vania@hsr.it.

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.

PMID:
25556566
PMCID:
PMC4297873
DOI:
10.1016/j.stemcr.2014.12.002
[Indexed for MEDLINE]
Free PMC Article

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