Shawn Kamboj, Erin L Carlson, Bradley P Ander, Kari L Hanson, Karl D Murray, Julie L Fudge, Melissa D Bauman, Cynthia M Schumann, Andrew S Fox
{"title":"从恒河猴和人类杏仁核亚核的细胞类型变异中获得转译启示","authors":"Shawn Kamboj, Erin L Carlson, Bradley P Ander, Kari L Hanson, Karl D Murray, Julie L Fudge, Melissa D Bauman, Cynthia M Schumann, Andrew S Fox","doi":"10.1176/appi.ajp.20230602","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Theories of amygdala function are central to our understanding of psychiatric and neurodevelopmental disorders. However, limited knowledge of the molecular and cellular composition of the amygdala impedes translational research aimed at developing new treatments and interventions. The aim of this study was to characterize and compare the composition of amygdala cells to help bridge the gap between preclinical models and human psychiatric and neurodevelopmental disorders.</p><p><strong>Methods: </strong>Tissue was dissected from multiple amygdala subnuclei in both humans (N=3, male) and rhesus macaques (N=3, male). Single-nucleus RNA sequencing was performed to characterize the transcriptomes of individual nuclei.</p><p><strong>Results: </strong>The results reveal substantial heterogeneity between regions, even when restricted to inhibitory or excitatory neurons. Consistent with previous work, the data highlight the complexities of individual marker genes for uniquely targeting specific cell types. Cross-species analyses suggest that the rhesus monkey model is well-suited to understanding the human amygdala, but also identify limitations. For example, a cell cluster in the ventral lateral nucleus of the amygdala (vLa) is enriched in humans relative to rhesus macaques. Additionally, the data describe specific cell clusters with relative enrichment of disorder-related genes. These analyses point to the human-enriched vLa cell cluster as relevant to autism spectrum disorder, potentially highlighting a vulnerability to neurodevelopmental disorders that has emerged in recent primate evolution. Further, a cluster of cells expressing markers for intercalated cells is enriched for genes reported in human genome-wide association studies of neuroticism, anxiety disorders, and depressive disorders.</p><p><strong>Conclusions: </strong>Together, these findings shed light on the composition of the amygdala and identify specific cell types that can be prioritized in basic science research to better understand human psychopathology and guide the development of potential treatments.</p>","PeriodicalId":7656,"journal":{"name":"American Journal of Psychiatry","volume":" ","pages":"1086-1102"},"PeriodicalIF":15.1000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Translational Insights From Cell Type Variation Across Amygdala Subnuclei in Rhesus Monkeys and Humans.\",\"authors\":\"Shawn Kamboj, Erin L Carlson, Bradley P Ander, Kari L Hanson, Karl D Murray, Julie L Fudge, Melissa D Bauman, Cynthia M Schumann, Andrew S Fox\",\"doi\":\"10.1176/appi.ajp.20230602\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>Theories of amygdala function are central to our understanding of psychiatric and neurodevelopmental disorders. However, limited knowledge of the molecular and cellular composition of the amygdala impedes translational research aimed at developing new treatments and interventions. The aim of this study was to characterize and compare the composition of amygdala cells to help bridge the gap between preclinical models and human psychiatric and neurodevelopmental disorders.</p><p><strong>Methods: </strong>Tissue was dissected from multiple amygdala subnuclei in both humans (N=3, male) and rhesus macaques (N=3, male). Single-nucleus RNA sequencing was performed to characterize the transcriptomes of individual nuclei.</p><p><strong>Results: </strong>The results reveal substantial heterogeneity between regions, even when restricted to inhibitory or excitatory neurons. Consistent with previous work, the data highlight the complexities of individual marker genes for uniquely targeting specific cell types. Cross-species analyses suggest that the rhesus monkey model is well-suited to understanding the human amygdala, but also identify limitations. For example, a cell cluster in the ventral lateral nucleus of the amygdala (vLa) is enriched in humans relative to rhesus macaques. Additionally, the data describe specific cell clusters with relative enrichment of disorder-related genes. These analyses point to the human-enriched vLa cell cluster as relevant to autism spectrum disorder, potentially highlighting a vulnerability to neurodevelopmental disorders that has emerged in recent primate evolution. Further, a cluster of cells expressing markers for intercalated cells is enriched for genes reported in human genome-wide association studies of neuroticism, anxiety disorders, and depressive disorders.</p><p><strong>Conclusions: </strong>Together, these findings shed light on the composition of the amygdala and identify specific cell types that can be prioritized in basic science research to better understand human psychopathology and guide the development of potential treatments.</p>\",\"PeriodicalId\":7656,\"journal\":{\"name\":\"American Journal of Psychiatry\",\"volume\":\" \",\"pages\":\"1086-1102\"},\"PeriodicalIF\":15.1000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American Journal of Psychiatry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1176/appi.ajp.20230602\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/10/30 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"PSYCHIATRY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1176/appi.ajp.20230602","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/30 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}
Translational Insights From Cell Type Variation Across Amygdala Subnuclei in Rhesus Monkeys and Humans.
Objective: Theories of amygdala function are central to our understanding of psychiatric and neurodevelopmental disorders. However, limited knowledge of the molecular and cellular composition of the amygdala impedes translational research aimed at developing new treatments and interventions. The aim of this study was to characterize and compare the composition of amygdala cells to help bridge the gap between preclinical models and human psychiatric and neurodevelopmental disorders.
Methods: Tissue was dissected from multiple amygdala subnuclei in both humans (N=3, male) and rhesus macaques (N=3, male). Single-nucleus RNA sequencing was performed to characterize the transcriptomes of individual nuclei.
Results: The results reveal substantial heterogeneity between regions, even when restricted to inhibitory or excitatory neurons. Consistent with previous work, the data highlight the complexities of individual marker genes for uniquely targeting specific cell types. Cross-species analyses suggest that the rhesus monkey model is well-suited to understanding the human amygdala, but also identify limitations. For example, a cell cluster in the ventral lateral nucleus of the amygdala (vLa) is enriched in humans relative to rhesus macaques. Additionally, the data describe specific cell clusters with relative enrichment of disorder-related genes. These analyses point to the human-enriched vLa cell cluster as relevant to autism spectrum disorder, potentially highlighting a vulnerability to neurodevelopmental disorders that has emerged in recent primate evolution. Further, a cluster of cells expressing markers for intercalated cells is enriched for genes reported in human genome-wide association studies of neuroticism, anxiety disorders, and depressive disorders.
Conclusions: Together, these findings shed light on the composition of the amygdala and identify specific cell types that can be prioritized in basic science research to better understand human psychopathology and guide the development of potential treatments.
期刊介绍:
The American Journal of Psychiatry, dedicated to keeping psychiatry vibrant and relevant, publishes the latest advances in the diagnosis and treatment of mental illness. The journal covers the full spectrum of issues related to mental health diagnoses and treatment, presenting original articles on new developments in diagnosis, treatment, neuroscience, and patient populations.