瑞士苏黎世大学Sebastian Jessberger等研究人员合作发现，多模态转录组学揭示神经发生衰老轨迹以及齿状回的与年龄相关的区域性炎症。2025年1月6日，《自然—神经科学》杂志在线发表了这项成果。

研究人员使用单细胞RNA测序技术表征了神经发生细胞及其周围齿状回（DG）微环境的转录组特征，并识别了与神经发生衰老相关的分子变化，包括从静止神经干细胞（NSC）的激活到命运决定后代的成熟。

通过整合空间转录组数据，研究人员发现随着年龄的增长，炎症细胞侵入海马，并展示了早期发病的神经炎症如何降低神经发生活性。

这些数据揭示了NSC及其周围神经发生DG微环境在衰老过程中的分子动态，为理解衰老海马中的年龄相关分子变化提供了强有力的资源。

研究人员表示，哺乳动物DG参与某些形式的学习和记忆，且DG功能障碍与与年龄相关的疾病有关。尽管在DG中NSC持续生成新神经元，神经发生潜力在整个生命周期中得以维持，但随着年龄的增长，神经发生会下降，这与年龄相关的认知衰退和疾病密切相关。

附：英文原文

Title: Multimodal transcriptomics reveal neurogenic aging trajectories and age-related regional inflammation in the dentate gyrus

Author: Wu, Yicheng, Korobeynyk, Vladyslav I., Zamboni, Margherita, Waern, Felix, Cole, John Darby, Mundt, Sarah, Greter, Melanie, Frisn, Jonas, Llorens-Bobadilla, Enric, Jessberger, Sebastian

Issue&Volume: 2025-01-06

Abstract: The mammalian dentate gyrus (DG) is involved in certain forms of learning and memory, and DG dysfunction has been implicated in age-related diseases. Although neurogenic potential is maintained throughout life in the DG as neural stem cells (NSCs) continue to generate new neurons, neurogenesis decreases with advancing age, with implications for age-related cognitive decline and disease. In this study, we used single-cell RNA sequencing to characterize transcriptomic signatures of neurogenic cells and their surrounding DG niche, identifying molecular changes associated with neurogenic aging from the activation of quiescent NSCs to the maturation of fate-committed progeny. By integrating spatial transcriptomics data, we identified the regional invasion of inflammatory cells into the hippocampus with age and show here that early-onset neuroinflammation decreases neurogenic activity. Our data reveal the lifelong molecular dynamics of NSCs and their surrounding neurogenic DG niche with age and provide a powerful resource to understand age-related molecular alterations in the aging hippocampus.

DOI: 10.1038/s41593-024-01848-4

Source: https://www.nature.com/articles/s41593-024-01848-4