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Commentary
Modeling psychiatric disorders through reprogramming
Kristen J. Brennand, Fred H. Gage
Disease Models & Mechanisms 2012 5: 26-32; doi: 10.1242/dmm.008268
Kristen J. Brennand
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Fred H. Gage
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  • For correspondence: gage@salk.edu
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    Fig. 1.

    Cellular phenotypes of RTT. (A) hiPSC-derived neurons from RTT patients show decreased soma size. *P<0.0001, Student’s t-test. Adapted from Cheung et al. (Cheung et al., 2011), with permission. (B) RTT-hiPSC-derived neurons have reduced density of excitatory synapses along dendrites compared with neurons derived from healthy controls. The staining shows that hiPSC-derived neurons from RTT patients have fewer VGLUT1-positive glutamatergic synaptic puncta interspersed along MAP2-positive dendrites. (C) Tracking fluorescence intensity changes representing intracellular Ca2+ fluctuations provides evidence of reduced synaptic activity in RTT-hiPSC-derived neurons relative to controls. B and C are adapted from Marchetto et al. (Marchetto et al., 2010), with permission. ROI, region of interest; WT, wild type. Scale bar: 5 μm.

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    Fig. 2.

    Cellular phenotype of SCZD. Rabies virus transmission between neurons can be used to assay neuronal connectivity. SCZD-hiPSC-derived neurons show decreased transmission of a genetically engineered rabies virus designed specifically to indicate monosynaptic neuronal connectivity (Rabies-EnvAΔG-RFP). Adapted from Brennand et al. (Brennand et al., 2011), with permission. LV-SYNP-HTG, lentivirus expressing a fusion protein comprising histone 2B and green fluorescent protein, TVA and elements of the synapsin (SYN) promoter; used to label neurons for microscopic analysis. Scale bar: 80 μm.

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Commentary
Modeling psychiatric disorders through reprogramming
Kristen J. Brennand, Fred H. Gage
Disease Models & Mechanisms 2012 5: 26-32; doi: 10.1242/dmm.008268
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Commentary
Modeling psychiatric disorders through reprogramming
Kristen J. Brennand, Fred H. Gage
Disease Models & Mechanisms 2012 5: 26-32; doi: 10.1242/dmm.008268

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  • Top
  • Article
    • Abstract
    • Introduction
    • Reprogramming patient fibroblasts to induced pluripotent stem cells
    • Differentiating iPSCs to neurons
    • Phenotypes of psychiatric disorders can be identified in hiPSC-derived neurons
    • Limitations of hiPSC-based modeling of psychiatric disease
    • Direct reprogramming of fibroblasts to neurons
    • Conclusion
    • Acknowledgements
    • Footnotes
    • REFERENCES
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