Disease-specific differences in gene expression, mitochondrial function and mitochondria-endoplasmic reticulum interactions in iPSC-derived cerebral organoids and cortical neurons in schizophrenia and bipolar disorder
Abstract We compared transcriptomic profiles of cerebral organoids differentiated from induced pluripotent stem cells of eight schizophrenia and eight bipolar disorder patients to identify genes that were differentially expressed in cerebral organoids between two disorders. Gene ontology analysis sh...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Springer
2023-03-01
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| Series: | Discover Mental Health |
| Online Access: | https://doi.org/10.1007/s44192-023-00031-8 |
| _version_ | 1797865492031995904 |
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| author | Annie Kathuria Kara Lopez-Lengowski Donna McPhie Bruce M. Cohen Rakesh Karmacharya |
| author_facet | Annie Kathuria Kara Lopez-Lengowski Donna McPhie Bruce M. Cohen Rakesh Karmacharya |
| author_sort | Annie Kathuria |
| collection | DOAJ |
| description | Abstract We compared transcriptomic profiles of cerebral organoids differentiated from induced pluripotent stem cells of eight schizophrenia and eight bipolar disorder patients to identify genes that were differentially expressed in cerebral organoids between two disorders. Gene ontology analysis showed relative up-regulation in schizophrenia organoids of genes related to response to cytokines, antigen binding and clathrin-coated vesicles, while showing up-regulation in bipolar disorder of genes involved in calcium binding. Gene set enrichment analysis revealed enrichment in schizophrenia of genes involved in mitochondrial and oxidative phosphorylation while showing enrichment in bipolar disorder of genes involved in long term potentiation and neuro-transporters. We compared mitochondrial function in cerebral organoids from schizophrenia and bipolar disorder subjects and found that while schizophrenia organoids showed deficits in basal oxygen consumption rate and ATP production when compared to healthy control organoids, while bipolar disorder organoids did not show these deficits. Gene ontology analyses also revealed enrichment in bipolar disorder of genes in ion binding and regulation of transport. Experiments examining the interaction between mitochondria and endoplasmic reticulum in cortical neurons from bipolar disorder subjects showed a significantly lower number of contact sites between mitochondria and endoplasmic reticulum when compared to cortical neurons from schizophrenia patients. These results point to disease-specific deficits in mitochondrial respiration in schizophrenia and in mitochondrial-endoplasmic reticulum interactions in bipolar disorder. |
| first_indexed | 2024-04-09T23:08:40Z |
| format | Article |
| id | doaj.art-b5de54aafcac4329a0e15f309b2b6c19 |
| institution | Directory Open Access Journal |
| issn | 2731-4383 |
| language | English |
| last_indexed | 2024-04-09T23:08:40Z |
| publishDate | 2023-03-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Mental Health |
| spelling | doaj.art-b5de54aafcac4329a0e15f309b2b6c192023-03-22T10:32:44ZengSpringerDiscover Mental Health2731-43832023-03-013111510.1007/s44192-023-00031-8Disease-specific differences in gene expression, mitochondrial function and mitochondria-endoplasmic reticulum interactions in iPSC-derived cerebral organoids and cortical neurons in schizophrenia and bipolar disorderAnnie Kathuria0Kara Lopez-Lengowski1Donna McPhie2Bruce M. Cohen3Rakesh Karmacharya4Center for Genomic Medicine, Massachusetts General HospitalCenter for Genomic Medicine, Massachusetts General HospitalDepartment of Psychiatry, Harvard Medical SchoolDepartment of Psychiatry, Harvard Medical SchoolCenter for Genomic Medicine, Massachusetts General HospitalAbstract We compared transcriptomic profiles of cerebral organoids differentiated from induced pluripotent stem cells of eight schizophrenia and eight bipolar disorder patients to identify genes that were differentially expressed in cerebral organoids between two disorders. Gene ontology analysis showed relative up-regulation in schizophrenia organoids of genes related to response to cytokines, antigen binding and clathrin-coated vesicles, while showing up-regulation in bipolar disorder of genes involved in calcium binding. Gene set enrichment analysis revealed enrichment in schizophrenia of genes involved in mitochondrial and oxidative phosphorylation while showing enrichment in bipolar disorder of genes involved in long term potentiation and neuro-transporters. We compared mitochondrial function in cerebral organoids from schizophrenia and bipolar disorder subjects and found that while schizophrenia organoids showed deficits in basal oxygen consumption rate and ATP production when compared to healthy control organoids, while bipolar disorder organoids did not show these deficits. Gene ontology analyses also revealed enrichment in bipolar disorder of genes in ion binding and regulation of transport. Experiments examining the interaction between mitochondria and endoplasmic reticulum in cortical neurons from bipolar disorder subjects showed a significantly lower number of contact sites between mitochondria and endoplasmic reticulum when compared to cortical neurons from schizophrenia patients. These results point to disease-specific deficits in mitochondrial respiration in schizophrenia and in mitochondrial-endoplasmic reticulum interactions in bipolar disorder.https://doi.org/10.1007/s44192-023-00031-8 |
| spellingShingle | Annie Kathuria Kara Lopez-Lengowski Donna McPhie Bruce M. Cohen Rakesh Karmacharya Disease-specific differences in gene expression, mitochondrial function and mitochondria-endoplasmic reticulum interactions in iPSC-derived cerebral organoids and cortical neurons in schizophrenia and bipolar disorder Discover Mental Health |
| title | Disease-specific differences in gene expression, mitochondrial function and mitochondria-endoplasmic reticulum interactions in iPSC-derived cerebral organoids and cortical neurons in schizophrenia and bipolar disorder |
| title_full | Disease-specific differences in gene expression, mitochondrial function and mitochondria-endoplasmic reticulum interactions in iPSC-derived cerebral organoids and cortical neurons in schizophrenia and bipolar disorder |
| title_fullStr | Disease-specific differences in gene expression, mitochondrial function and mitochondria-endoplasmic reticulum interactions in iPSC-derived cerebral organoids and cortical neurons in schizophrenia and bipolar disorder |
| title_full_unstemmed | Disease-specific differences in gene expression, mitochondrial function and mitochondria-endoplasmic reticulum interactions in iPSC-derived cerebral organoids and cortical neurons in schizophrenia and bipolar disorder |
| title_short | Disease-specific differences in gene expression, mitochondrial function and mitochondria-endoplasmic reticulum interactions in iPSC-derived cerebral organoids and cortical neurons in schizophrenia and bipolar disorder |
| title_sort | disease specific differences in gene expression mitochondrial function and mitochondria endoplasmic reticulum interactions in ipsc derived cerebral organoids and cortical neurons in schizophrenia and bipolar disorder |
| url | https://doi.org/10.1007/s44192-023-00031-8 |
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