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Gut-derived inflammatory cytokines modulate olfactory perception through metabolic reprogramming of ensheathing glia.

ABSTRACT: Gut-derived inflammatory cytokines modulate olfactory perception through metabolic reprogramming of ensheathing glia.

PROVIDER: PRJNA708213 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13911970.fastq.gz	Fastqsanger.gz
	SRR13911971.fastq.gz	Fastqsanger.gz
	SRR13911972.fastq.gz	Fastqsanger.gz
	SRR13911973.fastq.gz	Fastqsanger.gz
	SRR13911974.fastq.gz	Fastqsanger.gz

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Gut-derived inflammatory cytokines modulate olfactory perception through metabolic reprogramming of ensheathing glia.

Project description:Infection-induced aversion against enteropathogens is a conserved sickness behavior that can promote host survival1-3. The etiology of this behavior remains poorly understood, but studies in Drosophila have linked olfactory and gustatory perception to avoidance behaviors against toxic microbes4-6. Whether and how enteric infections directly influence sensory perception to induce or modulate such behaviors remains unknown. Here we show that enteropathogen infection in Drosophila can modulate olfactory perception through metabolic reprogramming of ensheathing glia of the antennal lobe. This reprogramming depends on JAK/STAT signaling activation in ensheathing glia as a consequence of infection-induced Unpaired cytokine expression in the intestine. JAK/STAT signaling induces the expression of glial monocarboxylate transporters (MCTs) and the apolipoprotein glial lazarillo (Glaz), resulting in changes in glial lipid metabolism. This modulates olfaction sensitivity, promoting avoidance of bacteria-laced food and increasing animal survival. While transient in young animals, gut-induced metabolic reprogramming of ensheathing glia becomes constitutive in old animals due to age-related intestinal inflammation, contributing to an age-related decline in olfaction sensitivity. Our findings identify adaptive glial metabolic reprogramming by gut-derived cytokines as a mechanism causing lasting changes in neuronal activity in the aging animal.

2021-06-02 | GSE168530 | GEO

Olfactory sensory neuron-specific IGF1R knockout in mice results in increased smell perception, insulin resistance and adiposity

Project description:Olfaction is fundamental for survival but there is little known about the connection between smell perception and metabolism. In this study we implemented IGF1R knockout mice in the olfactory sensory neurons, by olfactory marker protetin (OMP) Cre specific recombination, and investigated metabolic parameters, smell perception and transcriptome sequencing. We could demonstrate that IGF1R knockout in the olfactory sensory neurons results in enhanced smell perception, insulin resistance under normal chow diet conditions and increased adiposity in mice fed control diet. Transcriptome analysis of the olfactory epithelium revealed differential expression of markers for mature and immature olfactory sensory neurons, being down-regulated and up- regulated respectively, pointing to differentiation-dependent changes that result in increased olfactory perception. Collectively, this study provides evidence that enhanced smell perception can result in insulin resistance and increased adiposity.

2017-05-22 | GSE85329 | GEO

Transcriptional profiling predicts overwhelming homology of Schwann cells, olfactory ensheating cells and Schwann cell-like glia

Project description:The objective of this study was to compare the transcriptomes of uninfected and canine distemper virus-infected Schwann cells, olfactory ensheating cells, central nervous system Schwann cell-like glia, and fibroblasts cultured under identical conditions in vitro.

2014-06-02 | E-MTAB-2061 | biostudies-arrayexpress

Insights into olfactory ensheathing cell development from a laser-microdissection and transcriptome-profiling approach

Project description:Olfactory ensheathing cells (OECs) are neural crest-derived glia that ensheath bundles of olfactory axons from their peripheral origins in the olfactory epithelium to their central targets in the olfactory bulb. We took an unbiased laser microdissection and differential RNA-seq approach, validated by in situ hybridisation, to identify candidate molecular mechanisms underlying mouse OEC development and differences with the neural crest-derived Schwann cells developing on other peripheral nerves. We identified 25 novel markers for developing OECs in the olfactory mucosa and/or the olfactory nerve layer surrounding the olfactory bulb, of which 15 were OEC-specific, i.e., not expressed by Schwann cells. One pan-OEC-specific gene, Ptprz1, encodes a receptor-like tyrosine phosphatase that blocks oligodendrocyte differentiation. Mutant analysis suggests Ptprz1 may also act as a brake on OEC differentiation, and that its loss disrupts olfactory axon targeting. Overall, our results provide new insights into OEC development and the diversification of neural crest-derived glia.

2020-06-02 | GSE138596 | GEO

Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia (scRNA-seq: olfactory mucosa)

Project description:A subset of COVID-19 patients exhibit altered olfactory function. Here we analyze bulk and single cell RNA-Seq datasets to identify cell types in the olfactory epithelium and olfactory bulb that express cell entry molecules that mediate infection by SARS-CoV-2 (CoV-2), the causal agent in COVID-19. We find that samples from whole olfactory mucosa in species including mouse and human express two key genes involved in CoV-2 entry, ACE2 and TMPRSS2. However, neither olfactory sensory neurons nor olfactory bulb neurons express these genes, which are instead expressed in support cells, stem cells, and perivascular cells. These findings suggest that CoV-2 infection of non-neuronal cell types leads to anosmia and related disturbances in odor perception in COVID-19 patients.

2020-07-30 | GSE151346 | GEO

Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia (scRNA-seq: olfactory bulb)

2020-07-30 | GSE148360 | GEO

Olfactory

Project description:Olfactory

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Single-cell transcriptomes of developing and adult olfactory receptor neurons in Drosophila

Project description:Recognition of environmental cues is essential for the survival of all organisms. Precise transcriptional changes occur to enable the generation and function of the neural circuits underlying sensory perception. To gain insight into these changes, we generated single-cell transcriptomes of Drosophila olfactory receptor neurons (ORNs), thermosensory and hygrosensory neurons from the third antennal segment at an early developmental and adult stage. We discovered that ORNs maintain expression of the same olfactory receptors across development. Using these receptors and computational approaches, we matched transcriptomic clusters corresponding to anatomically and physiologically defined neuronal types across multiple developmental stages. Cell-type-specific transcriptomes, in part, reflected axon trajectory choices in early development and sensory modality in adults. Our analysis also uncovered type specific and broadly expressed genes that could modulate adult sensory responses. Collectively, our data reveal important transcriptomic features of sensory neuron biology and provides a resource for future studies of their development and physiology.

2021-02-01 | GSE162121 | GEO

Persistent and transient olfactory deficits in COVID-19 are associated to inflammation and zinc homeostasis

Project description:The Coronavirus Disease 2019 (COVID-19) is mainly a respiratory syndrome that can affect multiple organ systems, causing a variety of symptoms. Among the most common and characteristic symptoms are deficits in smell and taste perception, which may last for weeks/months after COVID-19 diagnosis owing to mechanisms that are not fully elucidated. In order to identify the determinants of olfactory symptom persistence, we obtained olfactory mucosa (OM) from 21 subjects, grouped according to clinical criteria: i) with persistent olfactory symptoms; ii) with transient olfactory symptoms; iii) without olfactory symptoms; and iv) non-COVID-19 controls. Cells from the olfactory mucosa were harvested for transcriptome analyses. RNA-Seq assays showed that gene expression levels are altered for a long time after infection. The expression profile of micro RNAs appeared significantly altered after infection, but no relationship with olfactory symptoms was found. On the other hand, patients with persistent olfactory deficits displayed increased levels of expression of genes involved in the inflammatory response and zinc homeostasis, suggesting an association with persistent or transient olfactory deficits in individuals who experienced SARS-CoV-2 infection.

2023-07-11 | GSE209806 | GEO

Single cell RNA-sequencing reveals five subtypes of olfactory bulb-derived olfactory ensheathing cells that secrete Reelin

Project description:Olfactory ensheathing cells (OECs) are the only glial cells that support the olfactory sensory neurons which undergo adult neurogenesis and continually project their axons to glomeruli in the olfactory bulbs. We used single cell RNA sequencing to study the gene expression programs of OECs and to determine the diversity of purified OECs previously shown to promote spinal cord injury repair. Our analyses revealed five subtypes of OECs, each expressing unique marker genes and pathways indicative of progenitor, axonal regeneration, migration, or microglia-like functions. As expected, we found substantial overlap of OEC genes with those of Schwann cells, but also with astrocytes, oligodendrocytes and microglia. We experimentally confirmed the classic marker genes of the OEC subtypes and provide evidence that Reelin and Connective Tissue Growth Factors are secreted by multiple OEC subtypes. Our results support that adult OECs are a hybrid glia including some with progenitor characteristics and that they likely carry out diverse functions related to injury repair and axonal regeneration.

2022-10-13 | GSE215247 | GEO

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