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

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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 languageEnglish (US)
Pages (from-to)e662
JournalTranslational psychiatry
Volume5
DOIs
StatePublished - Oct 20 2015
Externally publishedYes

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ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

Cite this

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, e662. https://doi.org/10.1038/tp.2015.118