Department of Genetics, Washington University School of Medicine, 660 S. Euclid Ave, Saint Louis, MO, 63110, USA.
Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid Ave, Saint Louis, MO, 63110, USA.
Biol Sex Differ. 2024 Jun 7;15(1):47. doi: 10.1186/s13293-024-00622-2.
Sex differences in the brain may play an important role in sex-differential prevalence of neuropsychiatric conditions.
In order to understand the transcriptional basis of sex differences, we analyzed multiple, large-scale, human postmortem brain RNA-Seq datasets using both within-region and pan-regional frameworks.
We find evidence of sex-biased transcription in many autosomal genes, some of which provide evidence for pathways and cell population differences between chromosomally male and female individuals. These analyses also highlight regional differences in the extent of sex-differential gene expression. We observe an increase in specific neuronal transcripts in male brains and an increase in immune and glial function-related transcripts in female brains. Integration with single-nucleus data suggests this corresponds to sex differences in cellular states rather than cell abundance. Integration with case-control gene expression studies suggests a female molecular predisposition towards Alzheimer's disease, a female-biased disease. Autism, a male-biased diagnosis, does not exhibit a male predisposition pattern in our analysis.
Overall, these analyses highlight mechanisms by which sex differences may interact with sex-biased conditions in the brain. Furthermore, we provide region-specific analyses of sex differences in brain gene expression to enable additional studies at the interface of gene expression and diagnostic differences.
大脑中的性别差异可能在神经精神疾病的性别差异患病率中起重要作用。
为了了解性别差异的转录基础，我们使用区域内和泛区域框架分析了多个大规模的人类死后大脑 RNA-Seq 数据集。
我们在许多常染色体基因中发现了性别偏向转录的证据，其中一些为性染色体男性和女性个体之间的途径和细胞群体差异提供了证据。这些分析还突出了性别差异基因表达程度的区域差异。我们观察到男性大脑中特定神经元转录物的增加，以及女性大脑中与免疫和神经胶质功能相关的转录物的增加。与单细胞数据的整合表明，这与细胞状态的性别差异相对应，而不是细胞丰度的差异。与病例对照基因表达研究的整合表明，女性在分子上更容易患阿尔茨海默病，这是一种女性偏爱的疾病。在我们的分析中，自闭症，一种男性偏爱的诊断，并没有表现出男性易患的模式。
总体而言，这些分析强调了性别差异可能与大脑中性别偏向条件相互作用的机制。此外，我们提供了大脑基因表达中性别差异的区域特异性分析，以促进基因表达和诊断差异界面的进一步研究。
