Transcription factor-mediated reprogramming of fibroblasts to expandable, myelinogenic oligodendrocyte progenitor cells

被引:208
|
作者
Najm, Fadi J. [1 ]
Lager, Angela M. [1 ]
Zaremba, Anita [2 ]
Wyatt, Krysta [2 ]
Caprariello, Andrew V. [2 ]
Factor, Daniel C. [1 ]
Karl, Robert T. [1 ]
Maeda, Tadao [3 ]
Miller, Robert H. [2 ]
Tesar, Paul J. [1 ,2 ]
机构
[1] Case Western Reserve Univ, Sch Med, Dept Genet & Genome Sci, Cleveland, OH 44106 USA
[2] Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA
[3] Case Western Reserve Univ, Sch Med, Dept Ophthalmol & Visual Sci, Cleveland, OH USA
基金
美国国家卫生研究院;
关键词
CENTRAL-NERVOUS-SYSTEM; NEURAL STEM-CELLS; DIRECT CONVERSION; GROWTH-FACTOR; DOPAMINERGIC-NEURONS; MOUSE FIBROBLASTS; PRECURSOR CELLS; DEFINED FACTORS; DIFFERENTIATION; INDUCTION;
D O I
10.1038/nbt.2561
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Cell-based therapies for myelin disorders, such as multiple sclerosis and leukodystrophies, require technologies to generate functional oligodendrocyte progenitor cells. Here we describe direct conversion of mouse embryonic and lung fibroblasts to induced oligodendrocyte progenitor cells (iOPCs) using sets of either eight or three defined transcription factors. iOPCs exhibit a bipolar morphology and global gene expression profile consistent with bona fide OPCs. They can be expanded in vitro for at least five passages while retaining the ability to differentiate into multiprocessed oligodendrocytes. When transplanted to hypomyelinated mice, iOPCs are capable of ensheathing host axons and generating compact myelin. Lineage conversion of somatic cells to expandable iOPCs provides a strategy to study the molecular control of oligodendrocyte lineage identity and may facilitate neurological disease modeling and autologous remyelinating therapies.
引用
收藏
页码:426 / +
页数:10
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