Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

An Integrative Analysis Identified Schizophrenia-Associated Brain Cell Types and Gene Expression Changes

Version 1 : Received: 18 August 2022 / Approved: 18 August 2022 / Online: 18 August 2022 (10:54:05 CEST)

How to cite: Cai, W.; Song, W.; Liu, Z.; Maharjan, D.T.; Liang, J.; Lin, G.N. An Integrative Analysis Identified Schizophrenia-Associated Brain Cell Types and Gene Expression Changes . Preprints 2022, 2022080341 (doi: 10.20944/preprints202208.0341.v1). Cai, W.; Song, W.; Liu, Z.; Maharjan, D.T.; Liang, J.; Lin, G.N. An Integrative Analysis Identified Schizophrenia-Associated Brain Cell Types and Gene Expression Changes . Preprints 2022, 2022080341 (doi: 10.20944/preprints202208.0341.v1).

Abstract

Schizophrenia (SCZ) is a severe mental disorder that may result in hallucinations, delusions, and extremely disordered thinking. How each cell type in the brain contributes to SCZ occurrence is still unclear. Here, we leveraged the human dorsolateral prefrontal cortex bulk RNA-seq data, then used the RNA-seq deconvolution algorithm CIBERSORTx to generate SCZ brain single-cell RNA-seq data for a comprehensive analysis to understand SCZ-associated brain cell types and gene expression changes. Firstly, we observed that the proportions of brain cell types in SCZ differed from normal samples. Among these cell types, astrocyte, pericyte, and PAX6 cells were found to have a higher proportion in SCZ patients (astrocyte: SCZ = 0.163, Control = 0.145, P.adj = 4.9×10-4; pericyte: SCZ = 0.057, Control = 0.066, P.adj = 1.1×10-4; PAX6 : SCZ = 0.014, Control = 0.011, P.adj = 0.014), while the L5/6_IT_CAR3 cells and LAMP5 cells are the exact opposite (L5/6_IT_Car3 : SCZ = 0.102, Control = 0.108, P.adj = 0.016; LAMP5 : SCZ = 0.057, Control = 0.066, P.adj = 2.2×10-6). Next, we investigated gene expression in cell types and functional pathways in SCZ. We observed chemical synaptic transmission dysregulation in two types of GABAergic neurons (PVALB and LAMP5), and immune reaction involvement in GABAergic neurons (SST) and non-neuronal cell types (endothelial and oligodendrocyte). Furthermore, we observed that some differential expression genes from bulk RNA-seq displayed cell-type-specific abnormal in the expression of molecules in SCZ. Finally, the cell types with the SCZ-related transcriptomic changes could be considered to belong to the same module since we observed two major similar coordinated transcriptomic changes across these cell types. Together, our results offer novel insights into cellular heterogeneity and the molecular mechanisms underlying SCZ.

Keywords

Schizophrenia; cell types proportions; differential expression genes; functional pathways; CIBERSORTx

Subject

MEDICINE & PHARMACOLOGY, Psychiatry & Mental Health studies

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.

We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.