Single-Cell RNA-Seq of Mouse Olfactory Bulb Reveals Cellular Heterogeneity and Activity-Dependent Molecular Census of Adult-Born Neurons

Abstract

Summary: Cellular heterogeneity within the mammalian brain poses a challenge toward understanding its complex functions. Within the olfactory bulb, odor information is processed by subtypes of inhibitory interneurons whose heterogeneity and functionality are influenced by ongoing adult neurogenesis. To investigate this cellular heterogeneity and better understand adult-born neuron development, we utilized single-cell RNA sequencing and computational modeling to reveal diverse and transcriptionally distinct neuronal and nonneuronal cell types. We also analyzed molecular changes during adult-born interneuron maturation and uncovered developmental programs within their gene expression profiles. Finally, we identified that distinct neuronal subtypes are differentially affected by sensory experience. Together, these data provide a transcriptome-based foundation for investigating subtype-specific neuronal function in the olfactory bulb (OB), charting the molecular profiles that arise during the maturation and integration of adult-born neurons and how they dynamically change in an activity-dependent manner. : Using single-cell sequencing, Tepe et al. describe cellular heterogeneity in the mouse olfactory bulb, uncover markers for each cell type, and reveal differentially regulated genes in adult-born neurons. These findings provide a framework for studying cell-type-specific functions and circuit integration in the mammalian brain. Keywords: single-cell RNA-seq, adult neurogenesis, olfactory bulb, circuit integration, olfaction, lineage, development, interneuron, transcriptome