Traunmüller Lisa, Duffy Erin E, Liu Hanqing, Sanalidou Stella, Krüttner Sebastian, Assad Elena G, Sun Senmiao, Pajarillo Naeem S, Niu Nancy, Griffith Eric C, Greenberg Michael E
Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
Junior Fellow, Society of Fellows, Harvard University, Boston, MA, USA.
Nat Commun. 2025 Aug 21;16(1):7787. doi: 10.1038/s41467-025-63029-6.
Exposure to novel environments (NE) induces structural and functional changes in multiple brain areas, including the hippocampus, driven in part by changes in gene expression. However, the cell-type-specific transcriptional and chromatin responses to NE remain poorly understood. We employed single-nucleus multiomics and bulk RNA-seq of the hippocampal DG, CA3, and CA1 regions of male mice to profile gene expression and chromatin accessibility following NE exposure. We observed region-specific responses in excitatory neurons and diverse transcriptional changes in inhibitory and non-neuronal cells. NE-regulated genes were enriched for secreted factors, and their cell-type-specific receptor expression highlighted candidate signaling pathways involved in learning and memory. We identified thousands of cell-type-specific chromatin accessibility changes, with coordinated expression and accessibility patterns implicating FOS/AP-1 as a key regulator. These data provide a rich resource of chromatin accessibility and gene expression profiles across hippocampal cell types in response to NE, a physiological stimulus affecting learning and memory.
暴露于新环境（NE）会在包括海马体在内的多个脑区诱导结构和功能变化，部分是由基因表达的变化驱动的。然而，细胞类型特异性的转录和染色质对NE的反应仍知之甚少。我们对雄性小鼠海马齿状回（DG）、CA3和CA1区域进行了单核多组学和大量RNA测序，以分析NE暴露后的基因表达和染色质可及性。我们在兴奋性神经元中观察到区域特异性反应，在抑制性和非神经元细胞中观察到不同转录变化。NE调控的基因富含分泌因子，其细胞类型特异性受体表达突出了参与学习和记忆的候选信号通路。我们鉴定出数千种细胞类型特异性染色质可及性变化，协调的表达和可及性模式表明FOS/AP-1是关键调节因子。这些数据提供了丰富的染色质可及性和基因表达谱资源，涵盖海马体细胞类型对NE的反应，NE是一种影响学习和记忆的生理刺激。
