Adult single-nucleus neuronal transcriptomes of insulin signaling mutants reveal regulators of behavior and learning

• Published in: Cell genomics 2024-12, Vol.4 (12), p.100720, Article 100720
• Main Authors: St. Ange, Jonathan, Weng, Yifei, Kaletsky, Rachel, Stevenson, Morgan E., Moore, Rebecca S., Zhou, Shiyi, Murphy, Coleen T.
• Format: Article
• Language: English
• Subjects: adult neurons; Animals; AWC neurons; Behavior, Animal - physiology; Caenorhabditis elegans; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; chemosensory GPCR; daf-2; IIS; insulin; Insulin - genetics; Insulin - metabolism; Learning - physiology; learning and memory; Memory - physiology; Mutation; neuronal single-nucleus sequencing; Neurons - metabolism; peptidergic GPCR; Receptor, Insulin - genetics; Receptor, Insulin - metabolism; Signal Transduction - genetics; Transcriptome
• ISSN: 2666-979X; 2666-979X
• DOI: 10.1016/j.xgen.2024.100720

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. [Display omitted] •Day 1 adult worms exhibit behavioral and transcriptional differences from L4 larva•csGPCR expression patterns change greatly from L4 to day 1 adulthood•Daf-2 animals’ chemosensory neurons exhibit the most changes in gene expression•Transcriptional changes in the AWC are functionally linked to learning and memory St. Ange et al. provide a single-nucleus RNA sequencing atlas of adult wild-type and IIS mutant Caenorhabditis elegans neurons, identifying genes that turn on from L4 to adulthood, including GPCRs. Functional behavior experiments revealed the roles of genes expressed in single neurons, including previously unidentified IIS targets.