Two factor-based reprogramming of rodent and human fibroblasts into Schwann cells.
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.
Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy.|University of Milano-Bicocca, 20126 Milan, Italy.
Pietro Giuseppe
PG
Mazzara
Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy.
Luca
0000-0003-3975-9148
L
Massimino
Division of Neuroscience, Axo-glia Interactions Unit-INSPE, San Raffaele Institute, 20132 Milan, Italy.
Marta
M
Pellegatta
Department of Clinical and Biological Sciences, and Cavalieri Ottolenghi Neuroscience Institute, University of Turin, Ospedale San Luigi, 10043 Orbassano, Turin, Italy.
Giulia
G
Ronchi
SR-Tiget, Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, 20132 Milan, Italy.
Alessandra
A
Ricca
Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy.
Angelo
A
Iannielli
Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy.
Serena Gea
SG
Giannelli
Department of Neurology, Neurophysiology and Neurorehabilitation Unit-INSPE, San Raffaele Scientific Institute, 20132 Milan, Italy.
Marco
M
Cursi
Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy.
Cinzia
C
Cancellieri
Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy.
Alessandro
A
Sessa
Department of Neurology, Neurophysiology and Neurorehabilitation Unit-INSPE, San Raffaele Scientific Institute, 20132 Milan, Italy.
Ubaldo
U
Del Carro
Department of Neurology, Neuropathology Unit-INSPE, San Raffaele Scientific Institute, Via Olgettina 48, 20132 Milan, Italy.
Angelo
A
Quattrini
Department of Clinical and Biological Sciences, and Cavalieri Ottolenghi Neuroscience Institute, University of Turin, Ospedale San Luigi, 10043 Orbassano, Turin, Italy.
Stefano
S
Geuna
SR-Tiget, Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, 20132 Milan, Italy.
Angela
A
Gritti
Division of Neuroscience, Axo-glia Interactions Unit-INSPE, San Raffaele Institute, 20132 Milan, Italy.
Carla
C
Taveggia
Division of Neuroscience, San Raffaele Scientific Institute, 20132 Milan, Italy.|National Research Council (CNR), Institute of Neuroscience, 20129 Milan, Italy.
Vania
V
Broccoli
D000818:Animals; D001369:Axons / Q000502:physiology; D002460:Cell Line; D065150:Cellular Reprogramming / Q000235:genetics*; D018920:Coculture Techniques; D051767:Early Growth Response Protein 2 / Q000502:physiology*; D005347:Fibroblasts / Q000502:physiology*; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D009186:Myelin Sheath / Q000378:metabolism / Q000648:ultrastructure; D059348:Peripheral Nerve Injuries / Q000628:therapy; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D012377:Rodentia; D055757:SOXE Transcription Factors / Q000502:physiology*; D012583:Schwann Cells / Q000502:physiology* / Q000637:transplantation / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000166:cytology / Q000502:physiology; D012867:Skin / Q000166:cytology
D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; D055757:SOXE Transcription Factors; C527924:Sox10 protein, mouse