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

Juan Antonio García-León, Manoj Kumar, Ruben Boon, David Chau, Jennifer One, Esther Wolfs, Kristel Eggermont, Pieter Berckmans, Nilhan Gunhanlar, Femke de Vrij, Bas Lendemeijer, Benjamin Pavie, Nikky Corthout, Steven A. Kushner, José Carlos Dávila, Ivo Lambrichts, Wei Shou Hu, Catherine M. Verfaillie

Research output: Contribution to journalArticle

12 Scopus citations

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. In this article, García-León JA and colleagues demonstrate the generation of functional oligodendrocytes (OLs) from human pluripotent stem cells in a rapid and efficient manner by the single overexpression of SOX10. Generated OLs resemble primary OLs at the transcriptome level and can myelinate neurons both in vivo and in vitro. Neuron-OL co-cultures, adapted to high-throughput screening formats, responded to drugs affecting myelination.

Original languageEnglish (US)
Pages (from-to)655-672
Number of pages18
JournalStem Cell Reports
Volume10
Issue number2
DOIs
StatePublished - Feb 13 2018

Keywords

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

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