Single-nucleus transcriptomic analysis reveals the relationship between gene expression in oligodendrocyte lineage and major depressive disorder

• DOI: 10.1186/s12967-023-04727-x
• Publication Date: 2024-01-27T17:02:11Z
• Authors: Yinping Xie; Lijuan Chen; Leimin Wang; Tongou Liu; Yage Zheng; Lujia Si; Hailong Ge; Hong Xu; Ling Xiao; Gaohua Wang
• Keywords: MALAT1; Candidate gene; Lineage (genetic)

Abstract Background Major depressive disorder (MDD) is a common mental illness that affects millions of people worldwide and imposes heavy burden on individuals, families society. Previous studies MDD predominantly focused neurons employed bulk homogenates brain tissues. This paper aims to decipher the relationship between oligodendrocyte lineage (OL) development at single-cell resolution level. Methods Here, we present use guided regularized random forest (GRRF) algorithm explore single-nucleus RNA sequencing profiles (GSE144136) OL four developmental stages, which contains dorsolateral prefrontal cortex 17 healthy controls (HC) cases, generated by Nagy C et al. We prioritized ordered differentially expressed genes (DEGs) based al., could discriminate cells in stages two adjacent OL. further screened top-ranked distinguished HC stages. Moreover, estimated performance GRRF model via area under curve value. Additionally, validated pivotal candidate gene Malat1 animal models. Results found that, among onset (OPC2) possesses best predictive power for distinguishing MDD, long noncoding MALAT1 has importance value In addition, results fluorescence situ hybridization assay showed plays critical role occurrence depression. Conclusions Our work elucidates mechanism from perspective level provides novel insight into