Format

Send to

Choose Destination
Stem Cell Reports. 2018 Feb 13;10(2):655-672. doi: 10.1016/j.stemcr.2017.12.014. Epub 2018 Jan 11.

SOX10 Single Transcription Factor-Based Fast and Efficient Generation of Oligodendrocytes from Human Pluripotent Stem Cells.

Author information

1
Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven Stem Cell Institute, Herestraat 49, Onderwijs en Navorsing 4, Box 804, 3000 Leuven, Belgium. Electronic address: jgarleon@hotmail.com.
2
Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven Stem Cell Institute, Herestraat 49, Onderwijs en Navorsing 4, Box 804, 3000 Leuven, Belgium.
3
Department of Chemical Engineering and Materials Science, University of Minnesota, 421 Washington Avenue Southeast, Minneapolis, MN 55455, USA.
4
Laboratory of Morphology, Biomedical Research Institute (BIOMED), Hasselt University, Agoralaan, Building C, 3590 Diepenbeek, Belgium.
5
Department of Psychiatry, Erasmus MC, 3015 CE Rotterdam, the Netherlands.
6
VIB Center for Brain and Disease Research, VIB-Leuven, 3000 Leuven, Belgium; VIB Bio Imaging Core, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.
7
Department of Cell Biology, Genetics and Physiology, Faculty of Sciences, Research Biomedical Institute of Málaga (IBIMA), University of Málaga, Campus de Teatinos s/n, 29010 Málaga, Spain; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
8
Department of Development and Regeneration, Stem Cell Biology and Embryology, KU Leuven Stem Cell Institute, Herestraat 49, Onderwijs en Navorsing 4, Box 804, 3000 Leuven, Belgium. Electronic address: catherine.verfaillie@kuleuven.be.

Abstract

Scarce access to primary samples and lack of efficient protocols to generate oligodendrocytes (OLs) from human pluripotent stem cells (hPSCs) are hampering our understanding of OL biology and the development of novel therapies. Here, we demonstrate that overexpression of the transcription factor SOX10 is sufficient to generate surface antigen O4-positive (O4+) and myelin basic protein-positive OLs from hPSCs in only 22 days, including from patients with multiple sclerosis or amyotrophic lateral sclerosis. The SOX10-induced O4+ population resembles primary human OLs at the transcriptome level and can myelinate neurons in vivo. Using in vitro OL-neuron co-cultures, myelination of neurons by OLs can also be demonstrated, which can be adapted to a high-throughput screening format to test the response of pro-myelinating drugs. In conclusion, we provide an approach to generate OLs in a very rapid and efficient manner, which can be used for disease modeling, drug discovery efforts, and potentially for therapeutic OL transplantation.

KEYWORDS:

amyotrophic lateral sclerosis; disease modeling; drug screening; induced pluripotent stem cells (iPSCs); multiple sclerosis; myelination; oligodendrocyte

PMID:
29337119
PMCID:
PMC5830935
DOI:
10.1016/j.stemcr.2017.12.014
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center