Increased abundance of translation machinery in stem cell–derived neural progenitor cells from four schizophrenia patients

A. Topol; J. A. English; E. Flaherty; P. Rajarajan; B. J. Hartley; S. Gupta; F. Desland; S. Zhu; T. Goff; L. Friedman; J. Rapoport; D. Felsenfeld; G. Cagney; A. Mackay-Sim; J. N. Savas; B. Aronow; G. Fang; B. Zhang; D. Cotter; K. J. Brennand

doi:10.1038/TP.2015.118

Increased abundance of translation machinery in stem cell–derived neural progenitor cells from four schizophrenia patients

A. Topol, J. A. English, E. Flaherty, P. Rajarajan, B. J. Hartley, S. Gupta, F. Desland, S. Zhu, T. Goff, L. Friedman, J. Rapoport, D. Felsenfeld, G. Cagney, A. Mackay-Sim, J. N. Savas, B. Aronow, G. Fang, B. Zhang, D. Cotter, K. J. Brennand

Research output: Contribution to journal › Article › peer-review

47 Scopus citations

Abstract

The genetic and epigenetic factors contributing to risk for schizophrenia (SZ) remain unresolved. Here we demonstrate, for the first time, perturbed global protein translation in human-induced pluripotent stem cell (hiPSC)-derived forebrain neural progenitor cells (NPCs) from four SZ patients relative to six unaffected controls. We report increased total protein levels and protein synthesis, together with two independent sets of quantitative mass spectrometry evidence indicating markedly increased levels of ribosomal and translation initiation and elongation factor proteins, in SZ hiPSC NPCs. We posit that perturbed levels of global protein synthesis in SZ hiPSC NPCs represent a novel post-transcriptional mechanism that might contribute to disease progression.

Original language	English (US)
Article number	e662
Journal	Translational psychiatry
Volume	5
Issue number	10
DOIs	https://doi.org/10.1038/TP.2015.118
State	Published - Oct 2015
Externally published	Yes

ASJC Scopus subject areas

Psychiatry and Mental health
Cellular and Molecular Neuroscience
Biological Psychiatry

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10.1038/TP.2015.118

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Topol, A., English, J. A., Flaherty, E., Rajarajan, P., Hartley, B. J., Gupta, S., Desland, F., Zhu, S., Goff, T., Friedman, L., Rapoport, J., Felsenfeld, D., Cagney, G., Mackay-Sim, A., Savas, J. N., Aronow, B., Fang, G., Zhang, B., Cotter, D., & Brennand, K. J. (2015). Increased abundance of translation machinery in stem cell–derived neural progenitor cells from four schizophrenia patients. Translational psychiatry, 5(10), Article e662. https://doi.org/10.1038/TP.2015.118

Topol, A, English, JA, Flaherty, E, Rajarajan, P, Hartley, BJ, Gupta, S, Desland, F, Zhu, S, Goff, T, Friedman, L, Rapoport, J, Felsenfeld, D, Cagney, G, Mackay-Sim, A, Savas, JN, Aronow, B, Fang, G, Zhang, B, Cotter, D & Brennand, KJ 2015, 'Increased abundance of translation machinery in stem cell–derived neural progenitor cells from four schizophrenia patients', Translational psychiatry, vol. 5, no. 10, e662. https://doi.org/10.1038/TP.2015.118

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title = "Increased abundance of translation machinery in stem cell–derived neural progenitor cells from four schizophrenia patients",

abstract = "The genetic and epigenetic factors contributing to risk for schizophrenia (SZ) remain unresolved. Here we demonstrate, for the first time, perturbed global protein translation in human-induced pluripotent stem cell (hiPSC)-derived forebrain neural progenitor cells (NPCs) from four SZ patients relative to six unaffected controls. We report increased total protein levels and protein synthesis, together with two independent sets of quantitative mass spectrometry evidence indicating markedly increased levels of ribosomal and translation initiation and elongation factor proteins, in SZ hiPSC NPCs. We posit that perturbed levels of global protein synthesis in SZ hiPSC NPCs represent a novel post-transcriptional mechanism that might contribute to disease progression.",

author = "A. Topol and English, {J. A.} and E. Flaherty and P. Rajarajan and Hartley, {B. J.} and S. Gupta and F. Desland and S. Zhu and T. Goff and L. Friedman and J. Rapoport and D. Felsenfeld and G. Cagney and A. Mackay-Sim and Savas, {J. N.} and B. Aronow and G. Fang and B. Zhang and D. Cotter and Brennand, {K. J.}",

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AU - Desland, F.

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AU - Mackay-Sim, A.

AU - Savas, J. N.

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Increased abundance of translation machinery in stem cell–derived neural progenitor cells from four schizophrenia patients

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