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Phenotypic differences in hiPSC NPCs derived from patients with schizophrenia.

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Title: Phenotypic differences in hiPSC NPCs derived from patients with schizophrenia.
Authors: Brennand, K., Savas, J. N., Kim, Y., Tran, N., Simone, A., Hashimoto-Torii, K., Beaumont, K. G., Kim, H. J., Topol, A., Ladran, I., Abdelrahim, M., Matikainen-Ankney, B., Chao, S-h., Mrksich, M., Rakic, P., Fang, G., Zhang, B., Yates, J. R., Gage, F. H.
Source: Molecular Psychiatry. Mar2015, Vol. 20 Issue 3, p361-368. 8p.
Subjects: Pluripotent stem cells, Schizophrenia treatment, Cell culture, Progenitor cells, Genetic regulation
Abstract: Consistent with recent reports indicating that neurons differentiated in vitro from human-induced pluripotent stem cells (hiPSCs) are immature relative to those in the human brain, gene expression comparisons of our hiPSC-derived neurons to the Allen BrainSpan Atlas indicate that they most resemble fetal brain tissue. This finding suggests that, rather than modeling the late features of schizophrenia (SZ), hiPSC-based models may be better suited for the study of disease predisposition. We now report that a significant fraction of the gene signature of SZ hiPSC-derived neurons is conserved in SZ hiPSC neural progenitor cells (NPCs). We used two independent discovery-based approaches-microarray gene expression and stable isotope labeling by amino acids in cell culture (SILAC) quantitative proteomic mass spectrometry analyses-to identify cellular phenotypes in SZ hiPSC NPCs from four SZ patients. From our findings that SZ hiPSC NPCs show abnormal gene expression and protein levels related to cytoskeletal remodeling and oxidative stress, we predicted, and subsequently observed, aberrant migration and increased oxidative stress in SZ hiPSC NPCs. These reproducible NPC phenotypes were identified through scalable assays that can be applied to expanded cohorts of SZ patients, making them a potentially valuable tool with which to study the developmental mechanisms contributing to SZ. [ABSTRACT FROM AUTHOR]
Copyright of Molecular Psychiatry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Phenotypic differences in hiPSC NPCs derived from patients with schizophrenia.
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  Data: <searchLink fieldCode="AR" term="%22Brennand%2C+K%2E%22">Brennand, K.</searchLink><br /><searchLink fieldCode="AR" term="%22Savas%2C+J%2E+N%2E%22">Savas, J. N.</searchLink><br /><searchLink fieldCode="AR" term="%22Kim%2C+Y%2E%22">Kim, Y.</searchLink><br /><searchLink fieldCode="AR" term="%22Tran%2C+N%2E%22">Tran, N.</searchLink><br /><searchLink fieldCode="AR" term="%22Simone%2C+A%2E%22">Simone, A.</searchLink><br /><searchLink fieldCode="AR" term="%22Hashimoto-Torii%2C+K%2E%22">Hashimoto-Torii, K.</searchLink><br /><searchLink fieldCode="AR" term="%22Beaumont%2C+K%2E+G%2E%22">Beaumont, K. G.</searchLink><br /><searchLink fieldCode="AR" term="%22Kim%2C+H%2E+J%2E%22">Kim, H. J.</searchLink><br /><searchLink fieldCode="AR" term="%22Topol%2C+A%2E%22">Topol, A.</searchLink><br /><searchLink fieldCode="AR" term="%22Ladran%2C+I%2E%22">Ladran, I.</searchLink><br /><searchLink fieldCode="AR" term="%22Abdelrahim%2C+M%2E%22">Abdelrahim, M.</searchLink><br /><searchLink fieldCode="AR" term="%22Matikainen-Ankney%2C+B%2E%22">Matikainen-Ankney, B.</searchLink><br /><searchLink fieldCode="AR" term="%22Chao%2C+S-h%2E%22">Chao, S-h.</searchLink><br /><searchLink fieldCode="AR" term="%22Mrksich%2C+M%2E%22">Mrksich, M.</searchLink><br /><searchLink fieldCode="AR" term="%22Rakic%2C+P%2E%22">Rakic, P.</searchLink><br /><searchLink fieldCode="AR" term="%22Fang%2C+G%2E%22">Fang, G.</searchLink><br /><searchLink fieldCode="AR" term="%22Zhang%2C+B%2E%22">Zhang, B.</searchLink><br /><searchLink fieldCode="AR" term="%22Yates%2C+J%2E+R%2E%22">Yates, J. R.</searchLink><br /><searchLink fieldCode="AR" term="%22Gage%2C+F%2E+H%2E%22">Gage, F. H.</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Molecular+Psychiatry%22">Molecular Psychiatry</searchLink>. Mar2015, Vol. 20 Issue 3, p361-368. 8p.
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  Data: <searchLink fieldCode="DE" term="%22Pluripotent+stem+cells%22">Pluripotent stem cells</searchLink><br /><searchLink fieldCode="DE" term="%22Schizophrenia+treatment%22">Schizophrenia treatment</searchLink><br /><searchLink fieldCode="DE" term="%22Cell+culture%22">Cell culture</searchLink><br /><searchLink fieldCode="DE" term="%22Progenitor+cells%22">Progenitor cells</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+regulation%22">Genetic regulation</searchLink>
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  Data: Consistent with recent reports indicating that neurons differentiated in vitro from human-induced pluripotent stem cells (hiPSCs) are immature relative to those in the human brain, gene expression comparisons of our hiPSC-derived neurons to the Allen BrainSpan Atlas indicate that they most resemble fetal brain tissue. This finding suggests that, rather than modeling the late features of schizophrenia (SZ), hiPSC-based models may be better suited for the study of disease predisposition. We now report that a significant fraction of the gene signature of SZ hiPSC-derived neurons is conserved in SZ hiPSC neural progenitor cells (NPCs). We used two independent discovery-based approaches-microarray gene expression and stable isotope labeling by amino acids in cell culture (SILAC) quantitative proteomic mass spectrometry analyses-to identify cellular phenotypes in SZ hiPSC NPCs from four SZ patients. From our findings that SZ hiPSC NPCs show abnormal gene expression and protein levels related to cytoskeletal remodeling and oxidative stress, we predicted, and subsequently observed, aberrant migration and increased oxidative stress in SZ hiPSC NPCs. These reproducible NPC phenotypes were identified through scalable assays that can be applied to expanded cohorts of SZ patients, making them a potentially valuable tool with which to study the developmental mechanisms contributing to SZ. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Molecular Psychiatry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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