美国布朗大学Alexander Fleischmann小组的一项最新研究认为小鼠嗅觉皮层的单细胞基因组学揭示了与新皮层和祖先细胞类型进化特征的对比。这一研究成果于2025年4月8日发表在国际顶尖学术期刊《自然—神经科学》上。

研究小组进行了单核转录组和染色质可及性分析，以比较成年小鼠和四足动物物种的三层和六层皮质区域的神经元。研究团队发现，与六层新皮层相比，三层嗅觉皮层（梨状）的谷氨酸能神经元在转录组谱中表现出连续的而不是离散的变化。梨状和新皮质谷氨酸能细胞亚群具有保守的转录组谱，可通过不同的区域特异性表观遗传状态来区分。

此外，该研究组在梨状皮质中发现了一个突出的未成熟神经元群体，并观察到，与新皮质相反，实验室小鼠和野生小鼠的梨状皮质在谷氨酸能细胞之间表现出差异。最后，该研究团队发现梨状神经元与海龟、蜥蜴和蝾螈皮层神经元的转录组相似性大于与新皮层神经元的转录组相似性。总之，尽管与新皮层共同进化超过2亿年，但嗅觉皮层神经元保留了祖先皮层的分子特征。

研究人员表示，了解皮层细胞类型多样性的分子逻辑，有助于阐明皮层回路的功能和进化。

附：英文原文

Title: Single-cell genomics of the mouse olfactory cortex reveals contrasts with neocortex and ancestral signatures of cell type evolution

Author: Zeppilli, Sara, Gurrola, Alonso O., Demetci, Pinar, Brann, David H., Pham, Tuan M., Attey, Robin, Zilkha, Noga, Kimchi, Tali, Datta, Sandeep R., Singh, Ritambhara, Tosches, Maria A., Crombach, Anton, Fleischmann, Alexander

Issue&Volume: 2025-04-08

Abstract: Understanding the molecular logic of cortical cell-type diversity can illuminate cortical circuit function and evolution. Here, we performed single-nucleus transcriptome and chromatin accessibility analyses to compare neurons across three- to six-layered cortical areas of adult mice and across tetrapod species. We found that, in contrast to the six-layered neocortex, glutamatergic neurons of the three-layered mouse olfactory (piriform) cortex displayed continuous rather than discrete variation in transcriptomic profiles. Subsets of piriform and neocortical glutamatergic cells with conserved transcriptomic profiles were distinguished by distinct, area-specific epigenetic states. Furthermore, we identified a prominent population of immature neurons in piriform cortex and observed that, in contrast to the neocortex, piriform cortex exhibited divergence between glutamatergic cells in laboratory versus wild-derived mice. Finally, we showed that piriform neurons displayed greater transcriptomic similarity to cortical neurons of turtles, lizards and salamanders than to those of the neocortex. In summary, despite over 200 million years of coevolution alongside the neocortex, olfactory cortex neurons retain molecular signatures of ancestral cortical identity.

DOI: 10.1038/s41593-025-01924-3

Source: https://www.nature.com/articles/s41593-025-01924-3