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Functional Integration of Dopaminergic Neurons Directly Converted from Mouse Fibroblasts

Author(s)
Kim, Jongpil; Su, Susan C.; Wang, Haoyi; Cheng, Albert W.; Cassady, John P.; Lodato, Michael Anthony; Lengner, Christopher J.; Chung, Chee Yeun; Dawlaty, Meelad M.; Tsai, Li-Huei; Jaenisch, Rudolf; ... Show more Show less
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Abstract
Recent advances in somatic cell reprogramming have highlighted the plasticity of the somatic epigenome, particularly through demonstrations of direct lineage reprogramming of one somatic cell type to another by defined factors. However, it is not clear to what extent this type of reprogramming is able to generate fully functional differentiated cells. In addition, the activity of the reprogrammed cells in cell transplantation assays, such as those envisaged for cell-based therapy of Parkinson's disease (PD), remains to be determined. Here we show that ectopic expression of defined transcription factors in mouse tail tip fibroblasts is sufficient to induce Pitx3+ neurons that closely resemble midbrain dopaminergic (DA) neurons. In addition, transplantation of these induced DA (iDA) neurons alleviates symptoms in a mouse model of PD. Thus, iDA neurons generated from abundant somatic fibroblasts by direct lineage reprogramming hold promise for modeling neurodegenerative disease and for cell-based therapies of PD.
Date issued
2011-10
URI
http://hdl.handle.net/1721.1/92351
Department
Massachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences; Picower Institute for Learning and Memory; Whitehead Institute for Biomedical Research
Journal
Cell Stem Cell
Publisher
Elsevier
Citation
Kim, Jongpil, Susan C. Su, Haoyi Wang, Albert W. Cheng, John P. Cassady, Michael A. Lodato, Christopher J. Lengner, et al. “Functional Integration of Dopaminergic Neurons Directly Converted from Mouse Fibroblasts.” Cell Stem Cell 9, no. 5 (November 2011): 413–419. © 2011 Elsevier Inc.
Version: Final published version
ISSN
19345909

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