Background: Although a number of imprinted genes are known to be highly expressed in the brain, and in certain brain regions in particular, whether they are truly over-represented in the brain has never been formally tested. Using thirteen single-cell RNA sequencing datasets we systematically investigated imprinted gene over-representation at the organ, brain region, and cell-specific levels. Results: We established that imprinted genes are indeed over-represented in the adult brain, and in neurons particularly compared to other brain cell-types. We then examined brain-wide datasets to test enrichment within distinct brain regions and neuron subpopulations and demonstrated over-representation of imprinted genes in the hypothalamus, ventral midbrain, pons and medulla. Finally, using datasets focusing on these regions of enrichment, we identified hypothalamic neuroendocrine populations and the monoaminergic hindbrain neurons as specific hotspots of imprinted gene expression. Conclusions: These analyses provide the first robust assessment of the neural systems on which imprinted genes converge. Moreover, the unbiased approach, with each analysis informed by the findings of the previous level, permits highly informed inferences about the functions on which imprinted gene expression converges. Our findings indicate the neuronal regulation of motivated behaviours such as feeding and sleep, alongside the regulation of pituitary function as functional hotspots for imprinting, thus adding statistical rigour to prior assumptions and providing testable predictions for novel neural and behavioural phenotypes associated with specific genes and imprinted gene networks. In turn, this work sheds further light on the potential evolutionary drivers of genomic imprinting in the brain.

中文翻译：

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以单细胞分辨率探索小鼠大脑中印迹基因表达和富集的系统研究

背景：尽管已知许多印记基因在大脑中高度表达，特别是在某些大脑区域，但它们是否真的在大脑中过度表达从未被正式测试过。使用 13 个单细胞 RNA 测序数据集，我们系统地研究了印迹基因在器官、大脑区域和细胞特异性水平上的过度表达。结果：我们确定，与其他脑细胞类型相比，印记基因在成人大脑中确实过多，尤其是在神经元中。然后，我们检查了全脑数据集以测试不同大脑区域和神经元亚群内的富集，并证明了下丘脑、腹侧中脑、脑桥和髓质中印记基因的过度表现。最后，使用专注于这些富集区域的数据集，我们将下丘脑神经内分泌群和单胺能后脑神经元确定为印记基因表达的特定热点。结论：这些分析首次对印记基因汇聚的神经系统进行了稳健的评估。此外，不偏不倚的方法，每个分析都由前一级别的发现提供信息，允许对印记基因表达收敛的功能进行高度知情的推论。我们的研究结果表明，诸如进食和睡眠等动机行为的神经元调节，以及垂体功能的调节作为印记的功能热点，从而为先前的假设增加了统计严谨性，并为与特定基因和印记相关的新神经和行为表型提供了可测试的预测。基因网络。反过来，