論文 - 詳細
| RRC ID | 62331 |
|---|---|
| 著者 | Sawada T, Chater TE, Sasagawa Y, Yoshimura M, Fujimori-Tonou N, Tanaka K, Benjamin KJM, Paquola ACM, Erwin JA, Goda Y, Nikaido I, Kato T. |
| タイトル | Developmental excitation-inhibition imbalance underlying psychoses revealed by single-cell analyses of discordant twins-derived cerebral organoids. |
| ジャーナル | Mol Psychiatry |
| Abstract |
Despite extensive genetic and neuroimaging studies, detailed cellular mechanisms underlying schizophrenia and bipolar disorder remain poorly understood. Recent progress in single-cell RNA sequencing (scRNA-seq) technologies enables identification of cell-type-specific pathophysiology. However, its application to psychiatric disorders is challenging because of methodological difficulties in analyzing human brains and the confounds due to a lifetime of illness. Brain organoids derived from induced pluripotent stem cells (iPSCs) of the patients are a powerful avenue to investigate the pathophysiological processes. Here, we generated iPSC-derived cerebral organoids from monozygotic twins discordant for psychosis. scRNA-seq analysis of the organoids revealed enhanced GABAergic specification and reduced cell proliferation following diminished Wnt signaling in the patient, which was confirmed in iPSC-derived forebrain neuronal cells. Two additional monozygotic twin pairs discordant for schizophrenia also confirmed the excess GABAergic specification of the patients' neural progenitor cells. With a well-controlled genetic background, our data suggest that unbalanced specification of excitatory and inhibitory neurons during cortical development underlies psychoses. |
| 巻・号 | 25(11) |
| ページ | 2695-2711 |
| 公開日 | 2020-11-1 |
| DOI | 10.1038/s41380-020-0844-z |
| PII | 10.1038/s41380-020-0844-z |
| PMID | 32764691 |
| PMC | PMC7577852 |
| MeSH | Cerebral Cortex* / cytology Cerebral Cortex* / pathology Humans Induced Pluripotent Stem Cells / pathology Male Organoids* / cytology Organoids* / pathology Psychotic Disorders / genetics* Psychotic Disorders / pathology* Sequence Analysis, RNA Single-Cell Analysis* Twins, Monozygotic / genetics* Twins, Monozygotic / psychology* |
| IF | 12.384 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 82 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 409B2(HPS0076) |