Zhongguo cuzhong zazhi (Feb 2023)

基于单细胞转录组的围产期卒中性别差异原因探究 Analysis of the Underlying Causes of Sex Differences in Perinatal Stroke Based on the Single-cell Transcriptomics

  • 刘阳, 程丝, 吕天节, 王誉博, 王孟, 许喆, 石延枫, 李子孝, 王拥军

DOI
https://doi.org/10.3969/j.issn.1673-5765.2023.02.005
Journal volume & issue
Vol. 18, no. 2
pp. 169 – 174

Abstract

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目的 通过对人脑胚胎发育中期的血管组成细胞进行分析，探索围产期卒中性别差异的可能原因。 方法 对公开发表的性别相关全基因组关联分析（genome-wide association study，GWAS）结果和血管单细胞转录组进行联合分析，确定性别差异相关的细胞类型。通过基因差异表达分析和功能富集分析，确定性别对细胞功能的影响，分析围产期卒中性别差异产生的潜在原因。 结果 经过判定，在胚胎发育中期血管单细胞转录组数据集的7例样本中，有4例男性和3例女性。典型的周细胞（P=0.018）和处于分裂状态的壁细胞（P=0.011）的表达谱与生物学性别的GWAS关联基因显著相关，而平滑肌细胞、成纤维细胞和全部5种内皮细胞类型与性别GWAS关联基因无明显相关性。总计345个基因在男性周细胞中显著高表达、619个基因在女性周细胞中显著高表达，这些差异表达基因分别富集在独特的生物学通路中，也同时富集在细胞能量代谢相关通路中。 结论 周细胞具有很强的性别差异性，可能是围产期卒中性别差异产生的原因。 Abstract: Objective To investigate the underlying causes of sex differences in perinatal stroke, by analyzing the human embryonic brain vascular cells in second trimester. Methods The data of vascular single-cell transcriptome and biological sex-related genome-wide association study results were jointly analyzed, to determine the correlation between cell type and sex differences. The differential gene expression and functional enrichment analysis were performed to determine the impact of sex on cellular function, as well as the underlying causes of the sex differences in perinatal stroke. Results Among the 7 human second trimester brain vascular scRNA-seq dataset, there were 4 males and 3 females. Typical pericytes and mitotic mural cells are significantly associated with sex-related GWAS-associated genes (P=0.0118 and 0.011, respectively), while smooth muscle cells, fibroblasts and all 5 types of endothelial cells are not associated with sex-related GWAS-associated genes. A total of 345 genes are significantly highly expressed in male pericytes, and 619 genes are significantly highly expressed in female pericytes. These differentially expressed genes are enriched in unique biological processes, and also in common biological processes such as cell energy metabolism. Conclusions The pericytes possess strong sex difference, which may be the underlying cause of sex difference in perinatal stroke.

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