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Nat Commun. 2017 Feb 7;8:14088. doi: 10.1038/ncomms14088.

Two factor-based reprogramming of rodent and human fibroblasts into Schwann cells.

Author information

1
Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy.
2
University of Milano-Bicocca, 20126 Milan, Italy.
3
Division of Neuroscience, Axo-glia Interactions Unit-INSPE, San Raffaele Institute, 20132 Milan, Italy.
4
Department of Clinical and Biological Sciences, and Cavalieri Ottolenghi Neuroscience Institute, University of Turin, Ospedale San Luigi, 10043 Orbassano, Turin, Italy.
5
SR-Tiget, Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, 20132 Milan, Italy.
6
Department of Neurology, Neurophysiology and Neurorehabilitation Unit-INSPE, San Raffaele Scientific Institute, 20132 Milan, Italy.
7
Department of Neurology, Neuropathology Unit-INSPE, San Raffaele Scientific Institute, Via Olgettina 48, 20132 Milan, Italy.
8
National Research Council (CNR), Institute of Neuroscience, 20129 Milan, Italy.

Abstract

Schwann cells (SCs) generate the myelin wrapping of peripheral nerve axons and are promising candidates for cell therapy. However, to date a renewable source of SCs is lacking. In this study, we show the conversion of skin fibroblasts into induced Schwann cells (iSCs) by driving the expression of two transcription factors, Sox10 and Egr2. iSCs resembled primary SCs in global gene expression profiling and PNS identity. In vitro, iSCs wrapped axons generating compact myelin sheaths with regular nodal structures. Conversely, iSCs from Twitcher mice showed a severe loss in their myelinogenic potential, demonstrating that iSCs can be an attractive system for in vitro modelling of PNS diseases. The same two factors were sufficient to convert human fibroblasts into iSCs as defined by distinctive molecular and functional traits. Generating iSCs through direct conversion of somatic cells offers opportunities for in vitro disease modelling and regenerative therapies.

PMID:
28169300
PMCID:
PMC5309703
DOI:
10.1038/ncomms14088
[Indexed for MEDLINE]
Free PMC Article

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