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

作者全名："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"

作者地址："[Wu, Jing; Li, Yifan; Huang, Yu; Liu, Lanxiang; Zhang, Hanping; Tan, Xunmin; Cheng, Ke; Liu, Yiyun; Pu, Juncai; Wang, Haiyang; Wu, Qingyuan; Xie, Peng] Chongqing Med Univ, Affiliated Hosp 1, NHC Key Lab Diag & Treatment Brain Funct Dis, Chongqing, Peoples R China; [Wu, Jing; Li, Yifan; Huang, Yu; Zhang, Hanping; Tan, Xunmin; Liu, Yiyun; Pu, Juncai; Wang, Haiyang; Zheng, Peng; Xie, Peng] Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, Chongqing, Peoples R China; [Wu, Jing; Li, Yifan; Huang, Yu; Liu, Lanxiang; Zhang, Hanping; Tan, Xunmin; Liu, Yiyun; Wang, Haiyang; Zheng, Peng; Xie, Peng] Jinfeng Lab, Chongqing, Peoples R China; [Liu, Lanxiang] Chongqing Med Univ, Yongchuan Hosp, Dept Neurol, Chongqing, Peoples R China; [Nagy, Corina; Turecki, Gustavo] Douglas Mental Hlth Univ Inst, McGill Grp Suicide Studies, Montreal, PQ, Canada; [Wu, Qingyuan] Chongqing Univ, Gorges Hosp 3, Dept Neurol, Chongqing, Peoples R China; [Perry, Seth W.; Wong, Ma-Li; Licinio, Julio] SUNY Upstate Med Univ, Coll Med, Dept Psychiat, Syracuse, NY USA; [Turecki, Gustavo] McGill Univ, Dept Human Genet, Montreal, PQ, Canada; [Turecki, Gustavo] Univ Toronto, Dept Psychiat, Toronto, ON, Canada"

通信作者："Xie, P (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, NHC Key Lab Diag & Treatment Brain Funct Dis, Chongqing, Peoples R China.; Zheng, P; Xie, P (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, Chongqing, Peoples R China.; Zheng, P; Xie, P (通讯作者)，Jinfeng Lab, Chongqing, Peoples R China."

来源：NATURE NEUROSCIENCE

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001027482600003

JCR分区：Q1

影响因子：21.2

年份：2023

卷号：26

期号：8

开始页：1352

结束页：+

文献类型：Article

关键词：　

摘要："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. The cellular and molecular mechanisms underlying major depressive disorder are unclear. Here, the authors report cell type- and cortical layer-specific gene expression changes and identify one microglia subpopulation associated with depressive-like behavior in female non-human primates."

基金机构："National Key Ramp;D Program of China [2017YFA0505700]; Projects of International Cooperation and Exchanges NSFC [81820108015]; Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences [2019PT320002]; Natural Science Foundation Project of China [81971296, 82171523, 82101596, 82201688, 82201683]; Chongqing Science and Technology Commission [cstc2019 jcyjjqX0009, cstc2021 jscx-msxm0026]; Program for Youth Innovation in Future Medicine, Chongqing Medical University; China Postdoctoral Science Foundation [2020TQ0393, 2021TQ0396, 2021MD703928, 2021MD693926, 2022MD713717]; Chongqing Talents Plan for Young Talents [CQYC202105017]; State University of New York (SUNY) Upstate Medical University"

基金资助正文："This work was supported by the National Key R & D Program of China (2017YFA0505700 to P.X.), Projects of International Cooperation and Exchanges NSFC (81820108015 to P.X.), Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences (2019PT320002 to P.X.), the Natural Science Foundation Project of China (81971296 and 82171523 to P.Z., 82101596 to J.P., 82201688 to J.W., 82201683 to L.L.), Chongqing Science and Technology Commission (cstc2019 jcyjjqX0009 to P.Z., cstc2021 jscx-msxm0026 to J.W.), Program for Youth Innovation in Future Medicine, Chongqing Medical University to P.Z., China Postdoctoral Science Foundation (2020TQ0393 to L.L., 2021TQ0396 and 2021MD703928 to H.Z., 2021MD693926 to H.W., 2022MD713717 to J.W.), Chongqing Talents Plan for Young Talents (CQYC202105017 to P.Z.) and institutional funds from the State University of New York (SUNY) Upstate Medical University. This paper is subject to the SUNY Open Access Policy. We thank J. Hu (ShanghaiTech University), T. F. Yuan (Shanghai Jiao Tong University), J. Yang and Y. He (Beijing Anding Hospital, Capital Medical University) for technical advice and helpful discussions."