TY - JOUR
T1 - Rapid single-step induction of functional neurons from human pluripotent stem cells
AU - Zhang, Yingsha
AU - Pak, Chang Hui
AU - Han, Yan
AU - Ahlenius, Henrik
AU - Zhang, Zhenjie
AU - Chanda, Soham
AU - Marro, Samuele
AU - Patzke, Christopher
AU - Acuna, Claudio
AU - Covy, Jason
AU - Xu, Wei
AU - Yang, Nan
AU - Danko, Tamas
AU - Chen, Lu
AU - Wernig, Marius
AU - Südhof, Thomas C.
N1 - Funding Information:
We would like to thank Drs. V. Sebastiano, B. Haddad, and B. Berninger for advice and reagents. This study was supported by grants from the Ellison Medical Foundation (AG-NS-0709-10 M.W.), the NIH (P50 AG010770-18A1 and R01 MH092931 to M.W. and T.C.S., and P50 MH086403 to L.C. and T.C.S.), the California Institute for Regenerative Medicine (RT2-02061 to M.W. and T.C.S.), and the Department of Defense (PR100175P1 to M.W.). M.W. is a New York Stem Cell Foundation-Robertson Investigator. N.Y. was supported by a fellowship from the Berry Foundation, H.A. by a fellowship from the Swedish Research Council and the Swedish Society for Medical Research, and C.P. by a fellowship from the Deutsche Forschungsgemeinschaft.
PY - 2013/6/5
Y1 - 2013/6/5
N2 - Available methods for differentiating human embryonic stem cells (ESCs) and induced pluripotent cells (iPSCs) into neurons are often cumbersome, slow, and variable. Alternatively, human fibroblasts can be directly converted into induced neuronal (iN) cells. However, with present techniques conversion is inefficient, synapse formation is limited, and only small amounts of neurons can be generated. Here, we show that human ESCs and iPSCs can be converted into functional iN cells with nearly 100% yield and purity in less than 2weeks by forced expression of a single transcription factor. The resulting ES-iN or iPS-iN cells exhibit quantitatively reproducible properties independent of the cell line of origin, form mature pre- and postsynaptic specializations, and integrate into existing synaptic networks when transplanted into mouse brain. As illustrated by selected examples, our approach enables large-scale studies of human neurons for questions such as analyses of human diseases, examination of human-specific genes, and drug screening
AB - Available methods for differentiating human embryonic stem cells (ESCs) and induced pluripotent cells (iPSCs) into neurons are often cumbersome, slow, and variable. Alternatively, human fibroblasts can be directly converted into induced neuronal (iN) cells. However, with present techniques conversion is inefficient, synapse formation is limited, and only small amounts of neurons can be generated. Here, we show that human ESCs and iPSCs can be converted into functional iN cells with nearly 100% yield and purity in less than 2weeks by forced expression of a single transcription factor. The resulting ES-iN or iPS-iN cells exhibit quantitatively reproducible properties independent of the cell line of origin, form mature pre- and postsynaptic specializations, and integrate into existing synaptic networks when transplanted into mouse brain. As illustrated by selected examples, our approach enables large-scale studies of human neurons for questions such as analyses of human diseases, examination of human-specific genes, and drug screening
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U2 - 10.1016/j.neuron.2013.05.029
DO - 10.1016/j.neuron.2013.05.029
M3 - Article
C2 - 23764284
AN - SCOPUS:84878849645
SN - 0896-6273
VL - 78
SP - 785
EP - 798
JO - Neuron
JF - Neuron
IS - 5
ER -