Cell-based therapy restores olfactory function in an inducible model of anosmia
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ABSTRACT:
PROVIDER: PRJNA512021 | ENA |
REPOSITORIES: ENA
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Project description:We explore culture coniditions that promote the expansion of engraftment-compentent olfactory basal progenitor cells in vitro.
2019-05-07 | GSE124443 | GEO
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 | GSE148360 | GEO
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
Project description:The pathophysiology of post-infectious and idiopathic olfactory loss is still poorly delineated. Since proteins are key players in olfaction and technical advances including LC-MS/MS mass spectrometry give us the opportunity for detailed analysis of the nasal mucus proteome we aimed to undertake a comparative analysis of the olfactory cleft mucus proteome using mucus samples of the olfactory cleft in patients with idiopathic and postinfectious olfactory disorders versus healthy controls. The study was conceived as a pilot study and included 7 patients with idiopathic hyp- and anosmia, 7 patients with postinfectious hyp- and anosmia and 7 healthy controls. In total, 1117 different proteins were detected in at least 5 patients in at least one group. No significant different overall protein concentrations in patients compared to healthy controls (0.4614 µg/µL, SD=0.26273 vs. 0.5143 µg/µL, SD=3087; p=0.689) were found. Significant correlation regarding olfactory test results (TDI score) and protein concentrations (r=0.114, p=0.623) were either found. Results of this study did not show significant differences regarding the proteomic composition of the olfactory cleft mucus between patients suffering from postinfectious and idiopathic dysosmia versus healthy controls. Thus, central olfactory processing pathways may play a role in idiopathic and postinfectious olfactory disorders.
2018-12-10 | PXD009172 | Pride
Project description:Stem cell-based therapies have been proposed as a strategy to replace damaged tissues, especially in the nervous system. A primary sensory modality, olfaction, is impaired in 12% of the US population, but lacks treatment options. We report here the development of a novel mouse model of inducible hyposmia and demonstrate that purified tissue-specific stem cells delivered intranasally engraft to produce olfactory neurons, achieving recovery of function. Adult mice were rendered hyposmic by conditional deletion of the ciliopathy-related IFT88 gene in the olfactory sensory neuron lineage and following experimentally induced olfactory injury, received either vehicle or stem cell infusion intranasally. Engraftment-derived olfactory neurons were identified histologically, and functional improvements were measured via electrophysiology and behavioral assay. We further explored mechanisms in culture that promote expansion of engraftment-competent adult olfactory basal progenitor cells. These findings provide a basis for translational research on propagating adult tissue-specific sensory progenitor cells and testing their therapeutic potential.
| S-EPMC6565856 | biostudies-literature
Project description:Anosmia, the loss of smell, is a common and often the sole symptom of COVID-19. The onset of the sequence of pathobiological events leading to olfactory dysfunction remains obscure. Here, we have developed a postmortem bedside surgical procedure to harvest endoscopically samples of respiratory and olfactory mucosae and whole olfactory bulbs. Our cohort of 85 cases included COVID-19 patients who died a few days after infection with SARS-CoV-2, enabling us to catch the virus while it was still replicating. We found that sustentacular cells are the major target cell type in the olfactory mucosa. We failed to find evidence for infection of olfactory sensory neurons, and the parenchyma of the olfactory bulb is spared as well. Thus, SARS-CoV-2 does not appear to be a neurotropic virus. We postulate that transient insufficient support from sustentacular cells triggers transient olfactory dysfunction in COVID-19. Olfactory sensory neurons would become affected without getting infected.
2021-10-24 | GSE176080 | GEO
Project description:Genetic causes of congenital anosmia
| PRJNA988248 | ENA
Project description:Genetic causes of congenital anosmia
| PRJNA988249 | ENA
Project description:The olfactory bulb (OB) is a critical component of mammalian olfactory neuroanatomy. Beyond being the first and sole relay station for olfactory information to the rest of the brain, it also contains elaborate stereotypical circuitry that is considered essential for olfaction. Indeed, substantial lesions of the OB in rodents lead to anosmia. Here, we examined the circuitry that underlies olfaction in a mouse model with severe developmental degeneration of the OB. These mice could perform odor-guided tasks and even responded normally to innate olfactory cues. Despite the near total loss of the OB, piriform cortex in these mice responded to odors normally and its neural activity sufficed to decode odor identity. We found that sensory neurons expressthe full repertoire of olfactory receptors and their axons project primarily to the rudiments of the OB, but also ectopically, to olfactory cortical regions. Within the OB, the number of principal neurons was greatly reduced and the morphology of their dendrites was abnormal, extending over large regions within the OB. Glomerular organization was totally lost in the severe cases of OB degeneration and altered in the more conserved OBs, and the transcriptional profile of the glomerular layer was highly inflammatory. This study shows that olfactory functionality can be preserved despite reduced and aberrant circuitry that is missing many of the elements that are believed to be essential for olfaction, and may explain reported retention of olfaction in humans with degenerated OBs
2023-09-04 | GSE241951 | GEO
Project description:Various reports indicate an association between COVID-19 and anosmia, suggesting an infection of the olfactory sensory epithelium, and thus a possible direct virus access to the brain. To test this hypothesis, we generated RNA-seq libraries from human olfactory neuroepithelia, in which we found substantial expression of the genes coding for the virus receptor angiotensin-converting enzyme-2 (ACE2), and for the virus internalization enhancer TMPRSS2. We analyzed a human olfactory single-cell RNA-seq dataset and determined that sustentacular cells, which maintain the integrity of olfactory sensory neurons, express ACE2 and TMPRSS2. We then observed that the ACE2 protein was highly expressed in a subset of sustentacular cells in human and mouse olfactory tissues. Finally, we found ACE2 transcripts in specific brain cell types, both in mice and humans. Sustentacular cells thus represent a potential entry door for SARS-CoV-2 in a neuronal sensory system that is in direct connection with the brain.
2020-11-13 | GSE151973 | GEO