Prefrontal Granule Cell-Related Genes and Schizophrenia
Prefrontal Granule Cell-Related Genes and Schizophrenia
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前额叶颗粒细胞相关基因与精神分裂症
DOI：
10.1093/cercor/bhaa360
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Yu Chunshui
中科院分区：
文献类型：
--
作者：
Liu Huaigui;Xu Lixue;Fu Jilian;Su Qian;Liu Nana;Xu Jiayuan;Tang Jie;Li Wei;Zhao Fangshi;Ding Hao;Liu Feng;Qin Wen;Yu Chunshui
虽然前额叶皮质颗粒层和精神分裂症在灵长类动物中是独一无二的，尤其是人类，但它们之间的联系尚不清楚。在这里，我们测试了精神分裂症是否与人类PFC中颗粒细胞（GC）相关基因的表达谱相关。我们基于6个死后人脑的密集采样的基因表达数据，确定了14个候选GC相关基因，其表达水平沿着无颗粒区、非颗粒区、轻颗粒区和颗粒前额叶区的梯度逐渐增加，基于人PFC的单细胞RNA测序数据，这些GC相关基因在神经元中的表达是其他细胞类型的10倍以上。这些GC相关基因在功能上与突触传递和细胞发育和分化相关。确定的14 GC相关基因显着富集精神分裂症，但不是抑郁症和双相情感障碍。4个稳定的精神分裂症和GC相关基因的表达水平在空间上与精神分裂症患者和健康对照之间的PFC中的灰质体积差异相关。本研究提供了一组人类前额叶GC的候选基因，并将GC相关基因的表达谱与精神分裂症患者的前额叶结构损伤联系起来。
Although both the granular layer of the prefrontal cortex (PFC) and schizophrenia are unique in primates, especially humans, their linkage is unclear. Here, we tested whether schizophrenia is associated with expression profiles of the granule cell (GC)-related genes in the human PFC. We identified 14 candidate GC-related genes with gradually increased expression levels along the gradient of the agranular, dysgranular, light-granular, and granular prefrontal regions based on the densely sampled gene expression data of 6 postmortem human brains, and with more than 10-fold expression in neurons than other cell types based on the single-cell RNA-sequencing data of the human PFC. These GC-related genes were functionally associated with synaptic transmission and cell development and differentiation. The identified 14 GC-related genes were significantly enriched for schizophrenia, but not for depression and bipolar disorder. The expression levels of the 4 stable schizophrenia- and GC-related genes were spatially correlated with gray matter volume differences in the PFC between patients with schizophrenia and healthy controls. This study provides a set of candidate genes for the human prefrontal GCs and links expression profiles of the GC-related genes to the prefrontal structural impairments in schizophrenia.