category
bioRxiv
date
Mar 5, 2026
slug
status
Published
summary
首次通过多模态技术(免疫组化、单核RNA测序、sf-CARS显微镜)系统解析钩束的分子细胞特征,发现抑郁症伴童年虐待组存在50个差异表达基因,揭示NECTIN3与MIR646的潜在调控关系,并发现年龄相关髓鞘化变化规律。
tags
单细胞测序
type
Post

📄 原文题目

A multimodal characterization of the human uncinate fasciculus

🔗 原文链接

💡 AI 核心解读

首次通过多模态技术(免疫组化、单核RNA测序、sf-CARS显微镜)系统解析钩束的分子细胞特征,发现抑郁症伴童年虐待组存在50个差异表达基因,揭示NECTIN3与MIR646的潜在调控关系,并发现年龄相关髓鞘化变化规律。

📝 英文原版摘要

The uncinate fasciculus (UF) is a hook-shaped long-range association white matter tract that serves to bidirectionally transmit information between the anterior temporal lobe and the orbitofrontal cortex. Neuroimaging studies have suggested that changes in UF microstructure are involved in the neurobiological sequalae of childhood abuse (CA). Given that the UF is not present in rodents, it is vastly understudied with no cellular and molecular information available. To this end, we aimed to perform a multimodal characterization of the UF between individuals diagnosed with depression who died by suicide with (DS-CA) and without a history of severe CA (DS) and psychiatrically healthy individuals (CTRL). Fresh frozen UF tissue was obtained from the Douglas Bell-Canada Brain Bank, with phenotypic information collected via psychological autopsy. Immunohistochemistry with PDGFR and NogoA was used to label oligodendrocyte precursor cell (OPC) and oligodendrocyte (OL), respectively, and stereology was performed to ascertain cell density and soma volume. Single nucleus RNA sequencing (snRNAseq) was used to generate a transcriptomic survey of the distinct cell types found in the UF. Finally, spectral focusing Coherent Anti-Stokes Raman Scattering (sf-CARS) microscopy was employed in tandem with a custom AxonDeepSeg segmentation model to measure axon diameter, myelin thickness, and g-ratio. No group differences were observed in histology or ultrastructure metrics, but nearly 50 differentially expressed genes (DEG) were identified between groups. Interestingly NECTIN3, the top DEG downregulated in OL1 and OL3 of DS-CA, is a computationally predicted target of the microRNA MIR646, the host gene of which was significantly downregulated in multiple cell types in DS-CA. Age-associated c
hanges were pronounced and observed in all modalities, including an age-related increase in OL density, extensive changes in glial gene expression, as well as decreases in axon diameter and g-ratio. This study serves as a foundational resource on the molecular and cellular properties of the human UF. Our results suggest that observable myelin-related traces of depression or CA are limited in the UF and highlights the need for future research on the cellular and molecular properties of white matter tracts during aging.
单核转录组学揭示细胞类型特异性重塑和癫痫相关的小胶质细胞系统性昼夜节律烟酸核苷(NaR)信号通过预折叠复合物参与未折叠蛋白反应和脂肪生成
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