Functional integration of dopaminergic neurons directly converted from mouse fibroblasts

Jongpil Kim, Susan C. Su, Haoyi Wang, Albert W. Cheng, John P. Cassady, Michael A. Lodato, Christopher J. Lengner, Chee Yeun Chung, Meelad M. Dawlaty, Li Huei Tsai, Rudolf Jaenisch

Research output: Contribution to journalArticle

174 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)413-419
Number of pages7
JournalCell Stem Cell
Volume9
Issue number5
DOIs
StatePublished - Nov 4 2011
Externally publishedYes

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Dopaminergic Neurons
Parkinson Disease
Fibroblasts
Cell- and Tissue-Based Therapy
Neurons
Cell Transplantation
Mesencephalon
Neurodegenerative Diseases
Tail
Transcription Factors
Transplantation

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine
  • Genetics

Cite this

Kim, J., Su, S. C., Wang, H., Cheng, A. W., Cassady, J. P., Lodato, M. A., ... Jaenisch, R. (2011). Functional integration of dopaminergic neurons directly converted from mouse fibroblasts. Cell Stem Cell, 9(5), 413-419. https://doi.org/10.1016/j.stem.2011.09.011

Functional integration of dopaminergic neurons directly converted from mouse fibroblasts. / Kim, Jongpil; Su, Susan C.; Wang, Haoyi; Cheng, Albert W.; Cassady, John P.; Lodato, Michael A.; Lengner, Christopher J.; Chung, Chee Yeun; Dawlaty, Meelad M.; Tsai, Li Huei; Jaenisch, Rudolf.

In: Cell Stem Cell, Vol. 9, No. 5, 04.11.2011, p. 413-419.

Research output: Contribution to journalArticle

Kim, J, Su, SC, Wang, H, Cheng, AW, Cassady, JP, Lodato, MA, Lengner, CJ, Chung, CY, Dawlaty, MM, Tsai, LH & Jaenisch, R 2011, 'Functional integration of dopaminergic neurons directly converted from mouse fibroblasts', Cell Stem Cell, vol. 9, no. 5, pp. 413-419. https://doi.org/10.1016/j.stem.2011.09.011
Kim, Jongpil ; Su, Susan C. ; Wang, Haoyi ; Cheng, Albert W. ; Cassady, John P. ; Lodato, Michael A. ; Lengner, Christopher J. ; Chung, Chee Yeun ; Dawlaty, Meelad M. ; Tsai, Li Huei ; Jaenisch, Rudolf. / Functional integration of dopaminergic neurons directly converted from mouse fibroblasts. In: Cell Stem Cell. 2011 ; Vol. 9, No. 5. pp. 413-419.
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