Conversion of mouse fibroblasts into oligodendrocyte progenitor-like cells through a chemical approach

• 来源期刊: 分子细胞生物学报（英文版）
• 年，卷（期）: 2019,（6）
• 页码范围: 489-495
• 页数: 7页
• 语种: 英文
• DOI: 10.1093/jmcb/mjy088

摘要

Transplantation of oligodendrocyte progenitor cells (OPCs) is a promising way for treating demyelinating diseases.However,generation of scalable and autologous sources of OPCs has proven difficult.We previously established a chemical condition M9 that could specifically initiate neural program in mouse embryonic fibroblasts.Here we found that M9 could induce the formation of colonies that undergo mesenchymal-to-epithelial transition at the early stage of reprogramming.These colonies may represent unstable and neural lineage-restricted intermediates that have not established a neural stem cell identity.By modulating the culture signaling recapitulating the principle of OPC development,these intermediate cells could be reprogrammed towards OPC fate.The chemical-induced OPC-like cells (ciOPLCs) resemble primary neural stem cell-derived OPCs in terms of their morphology,gene expression,and the ability of self-renewal.Upon differentiation,ciOPLCs could produce functional oligodendrocytes and myelinate the neuron axons in vitro,validating their OPC identity molecularly and functionally.Therefore,our study provides a non-integrating approach to OPC reprogramming that may ultimately provide an avenue to patient-specific cell-based or in situ regenerative therapy.