St Ange Jonathan, Weng Yifei, Kaletsky Rachel, Stevenson Morgan E, Moore Rebecca S, Zhou Shiyi, Murphy Coleen T
Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Cell Genom. 2024 Dec 11;4(12):100720. doi: 10.1016/j.xgen.2024.100720. Epub 2024 Dec 4.
Gene expression in individual neurons can change during development to adulthood and can have large effects on behavior. Additionally, the insulin/insulin-like signaling (IIS) pathway regulates many of the adult functions of Caenorhabditis elegans, including learning and memory, via transcriptional changes. We used the deep resolution of single-nucleus RNA sequencing to define the adult transcriptome of each neuron in wild-type and daf-2 mutants, revealing expression differences between L4 larval and adult neurons in chemoreceptors, synaptic genes, and learning/memory genes. We used these data to identify adult new AWC-specific regulators of chemosensory function that emerge upon adulthood. daf-2 gene expression changes correlate with improved cognitive functions, particularly in the AWC sensory neuron that controls learning and associative memory; behavioral assays of AWC-specific daf-2 genes revealed their roles in cognitive function. Combining technology and functional validation, we identified conserved genes that function in specific adult neurons to control behavior, including learning and memory.
在从发育到成年的过程中，单个神经元中的基因表达会发生变化，并且会对行为产生重大影响。此外，胰岛素/胰岛素样信号（IIS）通路通过转录变化调节秀丽隐杆线虫的许多成年功能，包括学习和记忆。我们利用单核RNA测序的深度分辨率来定义野生型和daf-2突变体中每个神经元的成年转录组，揭示了L4幼虫和成年神经元在化学感受器、突触基因以及学习/记忆基因方面的表达差异。我们利用这些数据来鉴定成年后出现的、新的、特定于AWC的化学感觉功能调节因子。daf-2基因表达的变化与认知功能的改善相关，特别是在控制学习和联想记忆的AWC感觉神经元中；对特定于AWC的daf-2基因进行的行为分析揭示了它们在认知功能中的作用。通过结合技术和功能验证，我们鉴定出了在特定成年神经元中发挥作用以控制行为（包括学习和记忆）的保守基因。
