Functional Integration of Dopaminergic Neurons Directly Converted from Mouse Fibroblasts
Name
Kim-2011-Functional Integrati.pdf
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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
Date Issued
October 2011
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
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.
MIT 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
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1016/j.stem.2011.09.011
