A molecular characterization and clinical relevance of microglia-like cells derived from patients with panic disorder
Abstract Few studies report the microglia involvement in the pathogenesis of panic disorder (PD), although the crucial role of microglia in other neuropsychiatric diseases is being emphasized. In addition, there is no report to characterize the phenotypic and functional levels of PD patient-derived...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-02-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-023-02342-4 |
| _version_ | 1811165692538388480 |
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| author | Min-Jung You Chan Rim Minji Bang Soyoung Sung Hui-Ju Kim Sang-Hyuk Lee Min-Soo Kwon |
| author_facet | Min-Jung You Chan Rim Minji Bang Soyoung Sung Hui-Ju Kim Sang-Hyuk Lee Min-Soo Kwon |
| author_sort | Min-Jung You |
| collection | DOAJ |
| description | Abstract Few studies report the microglia involvement in the pathogenesis of panic disorder (PD), although the crucial role of microglia in other neuropsychiatric diseases is being emphasized. In addition, there is no report to characterize the phenotypic and functional levels of PD patient-derived microglia to find their clinical relevance. Herein, we used a model to induce patient-derived microglia-like cells (iMGs) to clarify the molecular characteristics and function of PD-iMGs. We established iMGs from 17 PD patients and 16 healthy controls (non-psychiatric controls, HC). PD-iMGs showed increased T-cell death-associated gene-8 expression per the proposal of a previous in vivo study. In addition, we found that patient-derived iMGs showed reduced phagocytosis and increased TREM2 expression. We analyzed the phenotype of the PD-iMGs by RNA sequencing. The PD-iMGs clustered together distinct from HC-iMGs. Gene set enrichment analysis revealed the involvement of cholesterol biosynthesis and steroid metabolism in PD-iMGs. Regarding the cholesterol synthesis pathway, we discovered ACAT2 and DHCR7 as the most impacted genes related to a character of PD-iMGs compared to HC-iMGs. The ACAT2, a major cholesterol esterifier, was increased in PD-iMGs. Nevertheless, PD-iMGs did not show lipid droplet accumulation. Interestingly, ACAT2 expression was inversely correlated with the severity of depression and anxiety sensitivity to publicly observable anxiety reactions. We propose that microglia of PD patients have unique characteristics with dysregulation of cholesterol biosynthesis pathway and impaired phagocytosis, reflecting clinical phenotype. |
| first_indexed | 2024-04-10T15:40:45Z |
| format | Article |
| id | doaj.art-370fa326c1714ac3ba5b39f994f36ca3 |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-04-10T15:40:45Z |
| publishDate | 2023-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-370fa326c1714ac3ba5b39f994f36ca32023-02-12T12:23:26ZengNature Publishing GroupTranslational Psychiatry2158-31882023-02-0113111010.1038/s41398-023-02342-4A molecular characterization and clinical relevance of microglia-like cells derived from patients with panic disorderMin-Jung You0Chan Rim1Minji Bang2Soyoung Sung3Hui-Ju Kim4Sang-Hyuk Lee5Min-Soo Kwon6Department of Pharmacology, Research Institute for Basic Medical Science, School of Medicine, CHA UniversityDepartment of Pharmacology, Research Institute for Basic Medical Science, School of Medicine, CHA UniversityDepartment of Psychiatry, CHA Bundang Medical Center, CHA UniversityDepartment of Pharmacology, Research Institute for Basic Medical Science, School of Medicine, CHA UniversityDepartment of Pharmacology, Research Institute for Basic Medical Science, School of Medicine, CHA UniversityDepartment of Psychiatry, CHA Bundang Medical Center, CHA UniversityDepartment of Pharmacology, Research Institute for Basic Medical Science, School of Medicine, CHA UniversityAbstract Few studies report the microglia involvement in the pathogenesis of panic disorder (PD), although the crucial role of microglia in other neuropsychiatric diseases is being emphasized. In addition, there is no report to characterize the phenotypic and functional levels of PD patient-derived microglia to find their clinical relevance. Herein, we used a model to induce patient-derived microglia-like cells (iMGs) to clarify the molecular characteristics and function of PD-iMGs. We established iMGs from 17 PD patients and 16 healthy controls (non-psychiatric controls, HC). PD-iMGs showed increased T-cell death-associated gene-8 expression per the proposal of a previous in vivo study. In addition, we found that patient-derived iMGs showed reduced phagocytosis and increased TREM2 expression. We analyzed the phenotype of the PD-iMGs by RNA sequencing. The PD-iMGs clustered together distinct from HC-iMGs. Gene set enrichment analysis revealed the involvement of cholesterol biosynthesis and steroid metabolism in PD-iMGs. Regarding the cholesterol synthesis pathway, we discovered ACAT2 and DHCR7 as the most impacted genes related to a character of PD-iMGs compared to HC-iMGs. The ACAT2, a major cholesterol esterifier, was increased in PD-iMGs. Nevertheless, PD-iMGs did not show lipid droplet accumulation. Interestingly, ACAT2 expression was inversely correlated with the severity of depression and anxiety sensitivity to publicly observable anxiety reactions. We propose that microglia of PD patients have unique characteristics with dysregulation of cholesterol biosynthesis pathway and impaired phagocytosis, reflecting clinical phenotype.https://doi.org/10.1038/s41398-023-02342-4 |
| spellingShingle | Min-Jung You Chan Rim Minji Bang Soyoung Sung Hui-Ju Kim Sang-Hyuk Lee Min-Soo Kwon A molecular characterization and clinical relevance of microglia-like cells derived from patients with panic disorder Translational Psychiatry |
| title | A molecular characterization and clinical relevance of microglia-like cells derived from patients with panic disorder |
| title_full | A molecular characterization and clinical relevance of microglia-like cells derived from patients with panic disorder |
| title_fullStr | A molecular characterization and clinical relevance of microglia-like cells derived from patients with panic disorder |
| title_full_unstemmed | A molecular characterization and clinical relevance of microglia-like cells derived from patients with panic disorder |
| title_short | A molecular characterization and clinical relevance of microglia-like cells derived from patients with panic disorder |
| title_sort | molecular characterization and clinical relevance of microglia like cells derived from patients with panic disorder |
| url | https://doi.org/10.1038/s41398-023-02342-4 |
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