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Dopaminergic differentiation of schizophrenia hiPSCs

Molecular Psychiatry volume 20, pages 549–550 (2015)Cite this article

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Given the recent report that dopaminergic (DA) neurons are generated at extremely low efficiency from schizophrenia (SZ) patient-derived human-induced pluripotent stem cells (hiPSCs),1 it is important to communicate that we have successfully differentiated tyrosine hydroxylase (TH)-positive DA neurons from both SZ patients and controls at modest levels.

Robicsek et al.1 adopted a protocol whereby neural induction occurs via dual SMAD inhibition in a monolayer culture (using the bone morphogenetic protein inhibitor Noggin and the transforming growth factor beta inhibitor SB431542), followed by DA patterning through the addition of SHH for 5 days, and then SHH, fibroblast growth factor 8 (FGF8), brain-derived neurotrophic factor and ascorbic acid for 4 additional days (Supplementary Table 1).2 Using TH and dopamine transporter (DAT) as markers of DA neurons,1 the authors demonstrated a significant defect in the ability of the SZ hiPSC lines to differentiate to DA neurons. Within the mammalian brain, however, the expression of TH3 and DAT4, 5 is widespread and thus not solely indicative of the DA neuronal subtypes most relevant to SZ (reviewed in4).

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Figure 1

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Acknowledgements

Kristen Brennand is a New York Stem Cell Foundation - Robertson Investigator. The Brennand Laboratory is supported by a Brain and Behavior Young Investigator Grant, National Institute of Health (NIH) grant R01 MH101454 and the New York Stem Cell Foundation.

Author Contributions

As per our agreement with Coriell Cell Repository, many of the hiPSC lines generated from control and SZ fibroblasts will be available from Coriell. In addition, all control and SZ fibroblasts are in the process of being deposited with the NIMH RUCDR Repository.

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Authors and Affiliations

  1. Departments of Psychiatry and Neuroscience, Mount Sinai School of Medicine, New York, NY, USA

    B J Hartley, N Tran, I Ladran, K Reggio & K J Brennand

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  1. B J Hartley
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  2. N Tran
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  3. I Ladran
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Correspondence to K J Brennand.

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Hartley, B., Tran, N., Ladran, I. et al. Dopaminergic differentiation of schizophrenia hiPSCs. Mol Psychiatry 20, 549–550 (2015). https://doi.org/10.1038/mp.2014.194

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