小柯机器人

重庆医科大学第一附属医院Peng Xie和Peng Zheng共同合作，近期取得重要工作进展。他们通过整合空间和单核转录组数据阐明具有抑郁样行为雌性食蟹猴的小胶质细胞特异性反应。相关研究成果2023年7月13日在线发表于《自然—神经科学》杂志上。

据介绍，重度抑郁障碍是世界范围内一个严重的公共卫生挑战，然而，其潜在的细胞和分子机制大多是未知的。

研究人员使用单核RNA测序和空间转录组学对具有社交压力相关抑郁样行为的雌性食蟹猴的背外侧前额叶皮层进行了分析。研究人员发现，与抑郁样行为相关的基因表达变化主要发生在小胶质细胞中，研究人员报道了一个在抑郁样条件下富集的促炎小胶质细胞亚群。单核RNA测序数据鉴定了六个与抑郁样行为相关的富集基因模块，这些模块通过空间转录组学进一步解析。与挤在一起和独自坐着行为相关的基因模块在皮层浅层的神经元和少突胶质细胞中表达，而与运动和友好行为相关的遗传模块在皮层中深层的小胶质细胞和星形胶质细胞中富集。与抑郁样行为相关的小胶质细胞亚群在皮层深层富集。

总之，这一研究结果显示了雌性非人类灵长类动物的细胞类型和皮层特异性基因表达变化，并确定了一个与抑郁样行为相关的小胶质细胞亚群。

附：英文原文

Title: Integrating spatial and single-nucleus transcriptomic data elucidates microglial-specific responses in female cynomolgus macaques with depressive-like behaviors

Author: Wu, Jing, Li, Yifan, Huang, Yu, Liu, Lanxiang, Zhang, Hanping, Nagy, Corina, Tan, Xunmin, Cheng, Ke, Liu, Yiyun, Pu, Juncai, Wang, Haiyang, Wu, Qingyuan, Perry, Seth W., Turecki, Gustavo, Wong, Ma-Li, Licinio, Julio, Zheng, Peng, Xie, Peng

Issue&Volume: 2023-07-13

Abstract: Major depressive disorder represents a serious public health challenge worldwide; however, the underlying cellular and molecular mechanisms are mostly unknown. Here, we profile the dorsolateral prefrontal cortex of female cynomolgus macaques with social stress-associated depressive-like behaviors using single-nucleus RNA-sequencing and spatial transcriptomics. We find gene expression changes associated with depressive-like behaviors mostly in microglia, and we report a pro-inflammatory microglia subpopulation enriched in the depressive-like condition. Single-nucleus RNA-sequencing data result in the identification of six enriched gene modules associated with depressive-like behaviors, and these modules are further resolved by spatial transcriptomics. Gene modules associated with huddle and sit alone behaviors are expressed in neurons and oligodendrocytes of the superficial cortical layer, while gene modules associated with locomotion and amicable behaviors are enriched in microglia and astrocytes in mid-to-deep cortical layers. The depressive-like behavior associated microglia subpopulation is enriched in deep cortical layers. In summary, our findings show cell-type and cortical layer-specific gene expression changes and identify one microglia subpopulation associated with depressive-like behaviors in female non-human primates.

DOI: 10.1038/s41593-023-01379-4

Source: https://www.nature.com/articles/s41593-023-01379-4

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex