Accelerated generation of oligodendrocyte progenitor cells from human induced pluripotent stem cells by forced expression of Sox10 and Olig2.

Pengyan Li,Y. Alex Zhang,Zhiguo Chen,Xihe Tang,Mo Li,Shuyan Wang

doi:10.1007/s11427-016-0165-3

Abstract

Oligodendrocyte progenitor cells (OPCs) hold great promise for treatment of dysmyelinating disorders, such as multiple sclerosis and cerebral palsy. Recent studies on generation of human OPCs mainly use human embryonic stem cells (hESCs) or neural stem cells (NSCs) as starter cell sources for the differentiation process. However, NSCs are restricted in availability and the present method for generation of oligodendrocytes (OLs) from ESCs often requires a lengthy period of time. Here, we demonstrated a protocol to efficiently derive OPCs from human induced pluripotent stem cells (hiPSCs) by forced expression of two transcription factors (2TFs), Sox10 and Olig2. With this method, PDGFRα+ OPCs can be obtained in 14 days and O4+ OPCs in 56 days. Furthermore, OPCs may be able to differentiate to mature OLs that could ensheath axons when co-cultured with rat cortical neurons. The results have implications in the development of autologous cell therapies.

Highlights

The loss of OLs and myelin in the central nervous system (CNS) often causes substantial morbidity and mortality, such as multiple sclerosis and leukodystrophies
A subpopulation of the iPSCs-derived cells could proliferate in response to Oligodendrocyte progenitor cells (OPCs) medium added with PDGF and stained positive for PDGFRα—a defined specific marker for OPC (Sim et al, 2011; Wang et al, 2013), which was not expressed by iPSCs (Figure 1F)
We described a protocol to convert human induced pluripotent stem cells (hiPSCs) into OPCs by forced expression of two transcription factors, Sox10 and Olig2

Summary

Introduction

The loss of OLs and myelin in the central nervous system (CNS) often causes substantial morbidity and mortality, such as multiple sclerosis and leukodystrophies. OPCs can differentiate into OLs which ensheath axons with myelin during brain development and remyelinate axons after brain damage. OPCs have been identified as a promising cell population for therapeutic approaches in demyelinating diseases. Many studies have been focused on differentiation of OPCs from ESCs (Cloutier et al, 2006; Kang et al, 2007; Piao et al, 2015) and NSCs (Hwang et al, 2009; Sher et al, 2009), or generation of OPCs by direct lineage conversion for the treatment of those diseases (Najm et al, 2013; Yang et al, 2013). Grafts of OPCs derived from hESCs are allogeneic and may require immunosuppressive treatment after transplantation, apart from the ethical concerns associated with hESCs. Human NSCs (hNSCs) exist at the subven-

Methods

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Conclusion