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Generation of oligodendroglial cells by direct lineage conversion

Yang, Nan ; Zuchero, J. Bradley ; Ahlenius, Henrik LU ; Marro, Samuele ; Ng, Yi Han ; Vierbuchen, Thomas ; Hawkins, John S. ; Geissler, Richard ; Barres, Ben A. and Wernig, Marius (2013) In Nature Biotechnology 31(5). p.434-439
Abstract

Transplantation of oligodendrocyte precursor cells (OPCs) is a promising potential therapeutic strategy for diseases affecting myelin. However, the derivation of engraftable OPCs from human pluripotent stem cells has proven difficult and primary OPCs are not readily available. Here we report the generation of induced OPCs (iOPCs) by direct lineage conversion. Forced expression of the three transcription factors Sox10, Olig2 and Zfp536 was sufficient to reprogram mouse and rat fibroblasts into iOPCs with morphologies and gene expression signatures resembling primary OPCs. More importantly, iOPCs gave rise to mature oligodendrocytes that could ensheath multiple host axons when co-cultured with primary dorsal root ganglion cells and formed... (More)

Transplantation of oligodendrocyte precursor cells (OPCs) is a promising potential therapeutic strategy for diseases affecting myelin. However, the derivation of engraftable OPCs from human pluripotent stem cells has proven difficult and primary OPCs are not readily available. Here we report the generation of induced OPCs (iOPCs) by direct lineage conversion. Forced expression of the three transcription factors Sox10, Olig2 and Zfp536 was sufficient to reprogram mouse and rat fibroblasts into iOPCs with morphologies and gene expression signatures resembling primary OPCs. More importantly, iOPCs gave rise to mature oligodendrocytes that could ensheath multiple host axons when co-cultured with primary dorsal root ganglion cells and formed myelin after transplantation into shiverer mice. We propose direct lineage reprogramming as a viable alternative approach for the generation of OPCs for use in disease modeling and regenerative medicine.

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publishing date
type
Contribution to journal
publication status
published
in
Nature Biotechnology
volume
31
issue
5
pages
6 pages
publisher
Nature Publishing Group
external identifiers
  • pmid:23584610
  • scopus:84877329018
ISSN
1087-0156
DOI
10.1038/nbt.2564
language
English
LU publication?
no
id
5bd687f5-f411-4534-a336-fda83da3defd
date added to LUP
2025-08-26 11:22:01
date last changed
2025-08-26 13:00:48
@article{5bd687f5-f411-4534-a336-fda83da3defd,
  abstract     = {{<p>Transplantation of oligodendrocyte precursor cells (OPCs) is a promising potential therapeutic strategy for diseases affecting myelin. However, the derivation of engraftable OPCs from human pluripotent stem cells has proven difficult and primary OPCs are not readily available. Here we report the generation of induced OPCs (iOPCs) by direct lineage conversion. Forced expression of the three transcription factors Sox10, Olig2 and Zfp536 was sufficient to reprogram mouse and rat fibroblasts into iOPCs with morphologies and gene expression signatures resembling primary OPCs. More importantly, iOPCs gave rise to mature oligodendrocytes that could ensheath multiple host axons when co-cultured with primary dorsal root ganglion cells and formed myelin after transplantation into shiverer mice. We propose direct lineage reprogramming as a viable alternative approach for the generation of OPCs for use in disease modeling and regenerative medicine.</p>}},
  author       = {{Yang, Nan and Zuchero, J. Bradley and Ahlenius, Henrik and Marro, Samuele and Ng, Yi Han and Vierbuchen, Thomas and Hawkins, John S. and Geissler, Richard and Barres, Ben A. and Wernig, Marius}},
  issn         = {{1087-0156}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{434--439}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Biotechnology}},
  title        = {{Generation of oligodendroglial cells by direct lineage conversion}},
  url          = {{http://dx.doi.org/10.1038/nbt.2564}},
  doi          = {{10.1038/nbt.2564}},
  volume       = {{31}},
  year         = {{2013}},
}