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Cell Stem Cell. 2015 Aug 6;17(2):204-12. doi: 10.1016/j.stem.2015.07.006.

Direct Conversion of Normal and Alzheimer's Disease Human Fibroblasts into Neuronal Cells by Small Molecules.

Author information

1
State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, and Graduate School, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
2
Institute of Neurobiology, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
3
Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China.
4
Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China.
5
Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, 320 Yueyang Road, Shanghai 200031, China.
6
State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, and Graduate School, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Translational Medical Center for Stem Cell Therapy, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China. Electronic address: jzhao@sibs.ac.cn.
7
State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, and Graduate School, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Collaborative Innovation Center for Brain Science, School of Life Science and Technology, Tongji University, Shanghai 200092, China. Electronic address: gpei@sibs.ac.cn.

Abstract

Neuronal conversion from human fibroblasts can be induced by lineage-specific transcription factors; however, the introduction of ectopic genes limits the therapeutic applications of such induced neurons (iNs). Here, we report that human fibroblasts can be directly converted into neuronal cells by a chemical cocktail of seven small molecules, bypassing a neural progenitor stage. These human chemical-induced neuronal cells (hciNs) resembled hiPSC-derived neurons and human iNs (hiNs) with respect to morphology, gene expression profiles, and electrophysiological properties. This approach was further applied to generate hciNs from familial Alzheimer's disease patients. Taken together, our transgene-free and chemical-only approach for direct reprogramming of human fibroblasts into neurons provides an alternative strategy for modeling neurological diseases and for regenerative medicine.

PMID:
26253202
DOI:
10.1016/j.stem.2015.07.006
[Indexed for MEDLINE]
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