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

Pietro Giuseppe Mazzara, Luca Massimino, Marta Pellegatta, Giulia Ronchi, Alessandra Ricca, Angelo Iannielli, Serena Gea Giannelli, Marco Cursi, Cinzia Cancellieri, Alessandro Sessa, Ubaldo Del Carro, Angelo Quattrini, Stefano Geuna, Angela Gritti, Carla Taveggia and Vania Broccoli ()
Additional contact information
Pietro Giuseppe Mazzara: San Raffaele Scientific Institute
Luca Massimino: San Raffaele Scientific Institute
Marta Pellegatta: Axo-glia Interactions Unit-INSPE, San Raffaele Institute
Giulia Ronchi: and Cavalieri Ottolenghi Neuroscience Institute, University of Turin, Ospedale San Luigi
Alessandra Ricca: SR-Tiget, Stem Cells and Gene Therapy, San Raffaele Scientific Institute
Angelo Iannielli: San Raffaele Scientific Institute
Serena Gea Giannelli: San Raffaele Scientific Institute
Marco Cursi: Neurophysiology and Neurorehabilitation Unit-INSPE, San Raffaele Scientific Institute
Cinzia Cancellieri: San Raffaele Scientific Institute
Alessandro Sessa: San Raffaele Scientific Institute
Ubaldo Del Carro: Neurophysiology and Neurorehabilitation Unit-INSPE, San Raffaele Scientific Institute
Angelo Quattrini: Neuropathology Unit-INSPE, San Raffaele Scientific Institute
Stefano Geuna: and Cavalieri Ottolenghi Neuroscience Institute, University of Turin, Ospedale San Luigi
Angela Gritti: SR-Tiget, Stem Cells and Gene Therapy, San Raffaele Scientific Institute
Carla Taveggia: Axo-glia Interactions Unit-INSPE, San Raffaele Institute
Vania Broccoli: San Raffaele Scientific Institute

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms14088

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