Increased abundance of translation machinery in stem cell-derived neural progenitor cells from four schizophrenia patients.
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.
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
A
A
Topol
Royal College of Surgeons in Ireland, Beaumont Hospital, Beaumont, Dublin, Ireland.
J A
JA
English
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
E
E
Flaherty
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
P
P
Rajarajan
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
B J
BJ
Hartley
Department of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
S
S
Gupta
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
F
F
Desland
Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
S
S
Zhu
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
T
T
Goff
Childhood Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
L
L
Friedman
Childhood Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
J
J
Rapoport
Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
D
D
Felsenfeld
UCD Conway Institute of Biomolecular and Biomedical Research, Dublin, Ireland.
G
G
Cagney
Eskitis Institute for Drug Discovery, Griffith University, Brisbane, QLD, Australia.
A
A
Mackay-Sim
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.
J N
JN
Savas
Department of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
B
B
Aronow
Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
G
G
Fang
Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
B
B
Zhang
Royal College of Surgeons in Ireland, Beaumont Hospital, Beaumont, Dublin, Ireland.
D
D
Cotter
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.|Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
K J
KJ
Brennand
D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D016548:Prosencephalon / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism*