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

PG Mazzara, L Massimino, Marta Pellegatta, G Ronchi, A Ricca, A Iannielli, SG Giannelli, M Cursi, Cinzia Cancellieri, A Sessa, U Del Carro, A Quattrini, S Geuna, A Gritti, C Taveggia, V Broccoli

Research output: Contribution to journalArticle

4 Citations (Scopus)

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. © The Author(s) 2017.
Original languageEnglish
Article number14088
JournalNature Communications
Volume8
DOIs
Publication statusPublished - 2017

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axons
rodents
Schwann Cells
fibroblasts
Fibroblasts
Rodentia
therapy
myelin sheath
Cells
myelin
gene expression
nerves
cells
Gene expression
mice
Skin
Transcription Factors
Myelin Sheath
Axons
Gene Expression Profiling

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Two factor-based reprogramming of rodent and human fibroblasts into Schwann cells. / Mazzara, PG; Massimino, L; Pellegatta, Marta; Ronchi, G; Ricca, A; Iannielli, A; Giannelli, SG; Cursi, M; Cancellieri, Cinzia; Sessa, A; Del Carro, U; Quattrini, A; Geuna, S; Gritti, A; Taveggia, C; Broccoli, V.

In: Nature Communications, Vol. 8, 14088, 2017.

Research output: Contribution to journalArticle

Mazzara, PG ; Massimino, L ; Pellegatta, Marta ; Ronchi, G ; Ricca, A ; Iannielli, A ; Giannelli, SG ; Cursi, M ; Cancellieri, Cinzia ; Sessa, A ; Del Carro, U ; Quattrini, A ; Geuna, S ; Gritti, A ; Taveggia, C ; Broccoli, V. / Two factor-based reprogramming of rodent and human fibroblasts into Schwann cells. In: Nature Communications. 2017 ; Vol. 8.
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AU - Massimino, L

AU - Pellegatta, Marta

AU - Ronchi, G

AU - Ricca, A

AU - Iannielli, A

AU - Giannelli, SG

AU - Cursi, M

AU - Cancellieri, Cinzia

AU - Sessa, A

AU - Del Carro, U

AU - Quattrini, A

AU - Geuna, S

AU - Gritti, A

AU - Taveggia, C

AU - Broccoli, V

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AB - 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. © The Author(s) 2017.

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