Comparative characterization of human induced pluripotent stem cells (hiPSC) derived from patients with schizophrenia and autism

Lena Marie Grunwald, Ricarda Stock, Kathrina Haag, Sandra Buckenmaier, Mark Christian Eberle, Dirk Wildgruber, Helena Storchak, Martin Kriebel, Stephanie Weißgraeber, Lisha Mathew, Yasmin Singh, Maarten Loos, Ka Wan Li, Udo Kraushaar, Andreas J. Fallgatter, Hansjürgen Volkmer

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Human induced pluripotent stem cells (hiPSC) provide an attractive tool to study disease mechanisms of neurodevelopmental disorders such as schizophrenia. A pertinent problem is the development of hiPSC-based assays to discriminate schizophrenia (SZ) from autism spectrum disorder (ASD) models. Healthy control individuals as well as patients with SZ and ASD were examined by a panel of diagnostic tests. Subsequently, skin biopsies were taken for the generation, differentiation, and testing of hiPSC-derived neurons from all individuals. SZ and ASD neurons share a reduced capacity for cortical differentiation as shown by quantitative analysis of the synaptic marker PSD95 and neurite outgrowth. By contrast, pattern analysis of calcium signals turned out to discriminate among healthy control, schizophrenia, and autism samples. Schizophrenia neurons displayed decreased peak frequency accompanied by increased peak areas, while autism neurons showed a slight decrease in peak amplitudes. For further analysis of the schizophrenia phenotype, transcriptome analyses revealed a clear discrimination among schizophrenia, autism, and healthy controls based on differentially expressed genes. However, considerable differences were still evident among schizophrenia patients under inspection. For one individual with schizophrenia, expression analysis revealed deregulation of genes associated with the major histocompatibility complex class II (MHC class II) presentation pathway. Interestingly, antipsychotic treatment of healthy control neurons also increased MHC class II expression. In conclusion, transcriptome analysis combined with pattern analysis of calcium signals appeared as a tool to discriminate between SZ and ASD phenotypes in vitro.

Original languageEnglish
Article number179
JournalTranslational Psychiatry
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019

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Induced Pluripotent Stem Cells
Autistic Disorder
Schizophrenia
Neurons
Gene Expression Profiling
Major Histocompatibility Complex
Colony-Forming Units Assay
Calcium
Phenotype
Routine Diagnostic Tests
Antipsychotic Agents
Genes

Cite this

Grunwald, Lena Marie ; Stock, Ricarda ; Haag, Kathrina ; Buckenmaier, Sandra ; Eberle, Mark Christian ; Wildgruber, Dirk ; Storchak, Helena ; Kriebel, Martin ; Weißgraeber, Stephanie ; Mathew, Lisha ; Singh, Yasmin ; Loos, Maarten ; Li, Ka Wan ; Kraushaar, Udo ; Fallgatter, Andreas J. ; Volkmer, Hansjürgen. / Comparative characterization of human induced pluripotent stem cells (hiPSC) derived from patients with schizophrenia and autism. In: Translational Psychiatry. 2019 ; Vol. 9, No. 1.
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abstract = "Human induced pluripotent stem cells (hiPSC) provide an attractive tool to study disease mechanisms of neurodevelopmental disorders such as schizophrenia. A pertinent problem is the development of hiPSC-based assays to discriminate schizophrenia (SZ) from autism spectrum disorder (ASD) models. Healthy control individuals as well as patients with SZ and ASD were examined by a panel of diagnostic tests. Subsequently, skin biopsies were taken for the generation, differentiation, and testing of hiPSC-derived neurons from all individuals. SZ and ASD neurons share a reduced capacity for cortical differentiation as shown by quantitative analysis of the synaptic marker PSD95 and neurite outgrowth. By contrast, pattern analysis of calcium signals turned out to discriminate among healthy control, schizophrenia, and autism samples. Schizophrenia neurons displayed decreased peak frequency accompanied by increased peak areas, while autism neurons showed a slight decrease in peak amplitudes. For further analysis of the schizophrenia phenotype, transcriptome analyses revealed a clear discrimination among schizophrenia, autism, and healthy controls based on differentially expressed genes. However, considerable differences were still evident among schizophrenia patients under inspection. For one individual with schizophrenia, expression analysis revealed deregulation of genes associated with the major histocompatibility complex class II (MHC class II) presentation pathway. Interestingly, antipsychotic treatment of healthy control neurons also increased MHC class II expression. In conclusion, transcriptome analysis combined with pattern analysis of calcium signals appeared as a tool to discriminate between SZ and ASD phenotypes in vitro.",
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Grunwald, LM, Stock, R, Haag, K, Buckenmaier, S, Eberle, MC, Wildgruber, D, Storchak, H, Kriebel, M, Weißgraeber, S, Mathew, L, Singh, Y, Loos, M, Li, KW, Kraushaar, U, Fallgatter, AJ & Volkmer, H 2019, 'Comparative characterization of human induced pluripotent stem cells (hiPSC) derived from patients with schizophrenia and autism' Translational Psychiatry, vol. 9, no. 1, 179. https://doi.org/10.1038/s41398-019-0517-3

Comparative characterization of human induced pluripotent stem cells (hiPSC) derived from patients with schizophrenia and autism. / Grunwald, Lena Marie; Stock, Ricarda; Haag, Kathrina; Buckenmaier, Sandra; Eberle, Mark Christian; Wildgruber, Dirk; Storchak, Helena; Kriebel, Martin; Weißgraeber, Stephanie; Mathew, Lisha; Singh, Yasmin; Loos, Maarten; Li, Ka Wan; Kraushaar, Udo; Fallgatter, Andreas J.; Volkmer, Hansjürgen.

In: Translational Psychiatry, Vol. 9, No. 1, 179, 01.12.2019.

Research output: Contribution to JournalArticleAcademicpeer-review

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AU - Grunwald, Lena Marie

AU - Stock, Ricarda

AU - Haag, Kathrina

AU - Buckenmaier, Sandra

AU - Eberle, Mark Christian

AU - Wildgruber, Dirk

AU - Storchak, Helena

AU - Kriebel, Martin

AU - Weißgraeber, Stephanie

AU - Mathew, Lisha

AU - Singh, Yasmin

AU - Loos, Maarten

AU - Li, Ka Wan

AU - Kraushaar, Udo

AU - Fallgatter, Andreas J.

AU - Volkmer, Hansjürgen

PY - 2019/12/1

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