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相关文章:Proc Natl Acad Sci U S A. 2011 Jun 21;108(25):10343-8.
* [9 W! A$ T3 O, C$ w* d$ mDirect conversion of human fibroblasts to dopaminergic neurons.
1 o# b8 }* |6 M' e5 BPfisterer U, Kirkeby A, Torper O, Wood J, Nelander J, Dufour A, Bj?rklund A, Lindvall O, Jakobsson J, Parmar M.# \- W. g, P( ?3 M
SourceDepartments of Experimental Medical Science and Clinical Sciences, Wallenberg Neuroscience Center, and Lund Stem Cell Center, Lund University, SE-221 84 Lund, Sweden.
& n' ?8 [- D! \2 N
+ h9 w4 P+ Q1 V- \1 NAbstract
2 I k+ Q7 | e# ], D. J9 x# uRecent reports demonstrate that somaticmouse cells can be directly2 X) j, R6 W4 q9 B& K! d
converted to othermature cell types by using combined expression# Y U ~4 |) j% T
of de?ned factors. Here we show that the same strategy can be
& `; z$ T( c. j7 S, L9 Eapplied to human embryonic and postnatal ?broblasts. By overex-$ E$ u0 A: z6 [5 |
pression of the transcription factors Ascl1, Brn2, and Myt1l, human
* F' Q- X+ D9 W4 G4 O l?broblasts were ef?ciently converted to functional neurons. We
% ? D8 ?8 K. p# G; b2 malso demonstrate that the converted neurons can be directed to-6 n8 J& ] u7 I: R0 \0 E6 w* h2 ? \
ward distinct functional neurotransmitter phenotypeswhen the ap-% T; `/ e; p: M6 w# @ Y ]
propriate transcriptional cues are provided together with the three7 R( w6 w% M+ N+ k
conversion factors. By combining expression of the three conversion
& D Y1 i* z# V. g- dfactors with expression of two genes involved in dopamine neuron: l$ l( D1 ~! ^; P
generation, Lmx1a and FoxA2, we could direct the phenotype of8 n3 A& W# W8 o: u
the converted cells toward dopaminergic neurons. Such subtype-
/ l q% S& V$ \speci?c induced neurons derived from human somatic cells could' q8 Z z$ p, X: V& h) p
be valuable for disease modeling and cell replacement therapy.
. J3 b* m) s0 o1 }+ iDirect conversion of human fibroblasts to dopaminergic neurons. 以及 Direct generation of functional dopaminergic neurons from mouse and human fibroblasts全文: |
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