Rapid Single-Step Induction of Functional Neurons from Human Pluripotent Stem Cells
By Yingsha Zhang, ChangHui Pak, Yan Han, H. Ahlenius, Zhenjie Zhang, Soham Chanda, Samuele G. Marro, Christopher Patzke, Claudio Acuna, Jason P. Covy and 6 more. Neuron, 2013
1,445 citations recorded by the source corpus.
Available methods for differentiating human embryonic (ES) and induced pluripotent stem (iPS) cells 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 ES and iPS cells can be converted into functional iN cells with nearly 100% yield and purity in less than two weeks 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.
Subfields: Biomedical Engineering, Cellular and Molecular Neuroscience, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/7f9ea37694af57d5efaa96a6c9d7ab73bfe313de
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In Cellular and Molecular Neuroscience
- Brent R. Stockwell
- M. Shokhirev
- P. Hsu
- Jennifer Oki
- Peter Lotfy
- Silvana Konermann
- Nicholas J. Brideau
In Molecular Biology
- P. Hsu
- Brent R. Stockwell
- Jian Wang
- M. Shokhirev
- Jennifer Oki
- Peter Lotfy
- Silvana Konermann
- Nicholas J. Brideau
Citations in the corpus
- Inhibition of neuronal ferroptosis protects hemorrhagic brain. (2017, methodology): “The iPSC differentiation protocol was modified from the strategy reported by Zhang et al. (70).”
- Mitophagy and Alzheimer’s disease: cellular and molecular mechanisms (2017, background): “However, modelling neurodegenerative disease in an iPSC-derived neurons does come with significant challenges and iPSC-derived neurons may revert to embryonic phenotypes, which is a caveat when modelling late-onset disease [100, 101].”
- Transcriptome engineering with RNA-targeting Type VI-D CRISPR effectors (2018, positive): “Patient-derived human-induced pluripotent stem cells (hiPSCs) were differentiated into cortical neurons via Neurogenin-2 directed differentiation for 2 weeks (Zhang et al., 2013).”