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Single cell RNAseq of mouse olfactory bulb reveals cellular heterogeneity and activity dependent molecular census of adult-born neurons

ABSTRACT: Cellular heterogeneity within the mammalian brain poses a challenge towards understanding its complex functions. Within the olfactory bulb (OB), odor information is processed by subtypes of inhibitory interneurons whose heterogeneity and functionality is influenced by ongoing adult neurogenesis. To investigate this cellular heterogeneity, and to better understand the developmental programs of adult-born neurons, we utilized single cell RNA sequencing and computational modeling to reveal diverse and transcriptionally distinct neuronal and non-neuronal cell types. We also analyzed molecular changes during adult-born interneuron maturation, and uncovered developmental programs within their gene expression profiles. Finally, we discovered 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 OB, charting the molecular profiles that arise during the maturation and integration of adult-born neurons, and documenting activity-dependent changes in the cellular composition of the olfactory system.

ORGANISM(S): Mus musculus

PROVIDER: GSE121891 | GEO | 2018/12/04

REPOSITORIES: GEO

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Project description:In this study, we demonstrate that insulin is produced not only in the mammalian pancreas but also in adult neuronal cells derived from hippocampus and olfactory bulb. Paracrine Wnt3 plays an essential role in promoting the active expression of insulin in both hippocampus and olfactory bulb-derived neural stem cells. Our analysis indicates that the balance between Wnt3, which triggers the expression of insulin via NeuroD1 transcription factor, and IGFBP-4, which inhibits the original Wnt3 action, is regulated depending on the diabetic status. We also show that adult neural progenitors derived from diabetic animals retain the ability to give rise to insulin-producing cells and that grafting neuronal progenitors into the pancreas of diabetic animals reduces glucose levels. This study provides an example of a simple and direct use of adult stem cells from one organ to another, without introducing additional inductive genes. In this study, we demonstrate that insulin is produced not only in the mammalian pancreas but also in adult neuronal cells derived from hippocampus and olfactory bulb. Paracrine Wnt3 plays an essential role in promoting the active expression of insulin in both hippocampus and olfactory bulb-derived neural stem cells. Our analysis indicates that the balance between Wnt3, which triggers the expression of insulin via NeuroD1 transcription factor, and IGFBP-4, which inhibits the original Wnt3 action, is regulated depending on the diabetic status. We also show that adult neural progenitors derived from diabetic animals retain the ability to give rise to insulin-producing cells and that grafting neuronal progenitors into the pancreas of diabetic animals reduces glucose levels. This study provides an example of a simple and direct use of adult stem cells from one organ to another, without introducing additional inductive genes. Total four different samples, gene expressions in hippocampal derived neural stem cells (HPC NSC), that in Olfactory bulb-derived neural stem cells (OB NSC), that in neurons derived from the HPC NSCs (HPC Neu) and that in neurons derived from the OB NSCs (OB Neu) were independently analyzed. Three independent experiments were performed to prepare each cell sample, and the extracted total RNAs from each cell source were mixed to apply following microarray analysis (Four independent RNA sample; HPC NSC, OB NSC, HPC Neu and OB Neu).

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Single cell RNAseq of mouse olfactory bulb reveals cellular heterogeneity and activity dependent molecular census of adult-born neurons

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