Cell type specific transcriptomic alterations in prefrontal deep-layer pyramidal neurons in individuals with a history of childhood abuse
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ABSTRACT:
PROVIDER: PRJNA660428 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12554226_1.fastq.gz | Fastqsanger.gz | |||
| SRR12554226_2.fastq.gz | Fastqsanger.gz | |||
| SRR12554227_1.fastq.gz | Fastqsanger.gz | |||
| SRR12554227_2.fastq.gz | Fastqsanger.gz | |||
| SRR12554228_1.fastq.gz | Fastqsanger.gz |
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Project description:Childhood abuse significantly increases the lifetime risk of negative mental health outcomes, including psychiatric disorders, such as depression and suicide. While clinical and epidemiological associations are well characterized, the molecular mechanisms through which adverse experiences in early life influence mental health outcomes over the lifespan remain unclear. In this study, we employed laser capture microdissection followed by RNA sequencing (LCM-seq) to investigate transcriptomic alterations to prefrontal deep-layer pyramidal neurons in individuals with a history of childhood abuse (N=24) in comparison to controls (N = 21). We first showed that LCM-seqproduced high-quality transcriptomic data that was strongly enriched for our cell type of interest (95.8% contribution). Differential expression analysis revealed119 genes that were altered between cases versus controls. Using weighted correlation network analysis (WGCNA) we next identified a network of downregulated genes, in individuals with a history of childhood abuse (r = -0.30, p = 0.04), that was enriched in pathways related to nervous system development and plasticity. The eigengene of this network was significantly correlated (r(23) = 0.490, p = 0.021) with average cell body volume of deep-layer pyramidal neurons. Of the 1042 mRNA genes within this network, 81 were differentially expressed between cases and controls. Using high-throughput qPCR, and comparing with an additional group of depressed subjects who died by suicide without a history of childhood abuse (N = 29), we found 7 genes whose expression levels were significantly (p < 0.05) predicted by a history of childhood abuse but not major depressive disorder and suicide.Our study, therefore, advances our understanding of the long term impact of childhood abuse and points to some of the molecular pathways that may underly previously observed alterations innervous system development and plasticity.
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