Functional integration of dopaminergic neurons directly converted from mouse fibroblasts.
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.
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Jongpil
J
Kim
Susan C
SC
Su
Haoyi
H
Wang
Albert W
AW
Cheng
John P
JP
Cassady
Michael A
MA
Lodato
Christopher J
CJ
Lengner
Chee-Yeun
CY
Chung
Meelad M
MM
Dawlaty
Li-Huei
LH
Tsai
Rudolf
R
Jaenisch
D000818:Animals; D002454:Cell Differentiation; D059290:Dopaminergic Neurons / Q000166:cytology* / Q000378:metabolism* / Q000637:transplantation; D005347:Fibroblasts / Q000166:cytology*; D020869:Gene Expression Profiling; D051379:Mice; D010300:Parkinson Disease / Q000628:therapy; D014157:Transcription Factors / Q000378:metabolism
D014157:Transcription Factors