Bibliographic Details
| Title: |
Cellular Diversity in Human Subgenual Anterior Cingulate and Dorsolateral Prefrontal Cortex by Single-Nucleus RNASequencing. |
| Authors: |
Kim, Billy1, Dowon Kim1, Schulmann, Anton2, Patel, Yash1, Caban-Rivera, Carolina1, Kim, Paul1, Jambhale, Ananya1, Johnson, Kory R.3, Ningping Feng1, Qing Xu1, Sun Jung Kang4, Mandal, Ajeet1, Kelly, Michael5, Akula, Nirmala2, McMahon, Francis J.2, Lipska, Barbara1, Marenco, Stefano1 marencos@mail.nih.gov, Auluck, Pavan K.1 pavan.auluck@nih.gov |
| Source: |
Journal of Neuroscience. 5/10/2023, Vol. 43 Issue 19, p3582-3597. 16p. |
| Subject Terms: |
*CINGULATE cortex, *PREFRONTAL cortex, *GENOME-wide association studies, *GENE expression, *COGNITIVE development |
| Abstract: |
Regional cellular heterogeneity is a fundamental feature of the human neocortex; however, details of this heterogeneity are still undefined. We used single-nucleus RNA-sequencing to examine cell-specific transcriptional features in the dorsolateral PFC (DLPFC) and the subgenual anterior cingulate cortex (sgACC), regions implicated in major psychiatric disorders. Droplet-based nuclei-capture and library preparation were performed on replicate samples from 8 male donors without history of psychiatric or neurologic disorder. Unsupervised clustering identified major neural cell classes. Subsequent iterative clustering of neurons further revealed 20 excitatory and 22 inhibitory subclasses. Inhibitory cells were consistently more abundant in the sgACC and excitatory neuron subclusters exhibited considerable variability across brain regions. Excitatory cell subclasses also exhibited greater within-class transcriptional differences between the two regions. We used these molecular definitions to determine which cell classes might be enriched in loci carrying a genetic signal in genome-wide association studies or for differentially expressed genes in mental illness. We found that the heritable signals of psychiatric disorders were enriched in neurons and that, while the gene expression changes detected in bulk-RNA-sequencing studies were dominated by glial cells, some alterations could be identified in specific classes of excitatory and inhibitory neurons. Intriguingly, only two excitatory cell classes exhibited concomitant region-specific enrichment for both genome-wide association study loci and transcriptional dysregulation. In sum, by detailing the molecular and cellular diversity of the DLPFC and sgACC, we were able to generate hypotheses on regional and cell-specific dysfunctions that may contribute to the development of mental illness. [ABSTRACT FROM AUTHOR] |
|
Copyright of Journal of Neuroscience is the property of Society for Neuroscience and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
Academic Search Complete |
