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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE151346 | GEO | 2020/07/30

REPOSITORIES: GEO

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Project description:Olfactory sensory neurons distinguish a large variety of odor molecules and direct the information through their axons to the olfactory bulb, the first site for the processing of olfactory information in the brain. Olfaction is very important for most mammals for the maintenance of a good quality of life. Accumulating evidences endorse that olfactory sensory decline is connected with neurodegenerative disorders including schizophrenia, depression, multiple sclerosis, Huntington's, Alzheimer's and Parkinson's diseases. For several decades, neuroanatomical, volumetric, and histological approaches have been the gold standard techniques employed to characterize the olfactory bulb functionality. Diagnosis and treatment of olfactory dysfunction remain significant health care challenges to society. Novel strategies and clues that assist in the identification of biomarker and drug development for aid in the prevention and cure of neurological diseases are necessary. However, little attention has been focused specifically on the molecular composition of the olfactory bulb from the perspective of proteomics. To this end, an in-depth mapping of the olfactory bulb proteome was carried out using high resolution tandem mass spectrometry, revealing a repertoire of 7,754 proteins. A large proportion of the identified proteins were predicted to be involved in diverse biological processes including signal transduction, metabolism, transport, olfaction and protein synthesis. Pathway analysis of the identified proteins shows that, these proteins are predominantly involved in metabolic and neural processes, chromatin modeling, and synaptic vesicle transport associated with neuronal transmission. In total, our study offers valuable understandings into the molecular composition of the human olfactory bulb proteome that could possibly help neuroscience community to understand the olfactory bulb better and open avenues for intervention strategies for olfactory dysfunction in the future.

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

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