Dataset Information

Cultured Mesenchymal Cells from Nasal Turbinate as a Cellular Model of the Neurodevelopmental Component of Schizophrenia Etiology.

ABSTRACT: Study of the neurodevelopmental molecular mechanisms of schizophrenia requires the development of adequate biological models such as patient-derived cells and their derivatives. We previously used cell lines with neural progenitor properties (CNON) derived from superior or middle turbinates of patients with schizophrenia and control groups to study gene expression specific to schizophrenia. In this study, we compared single cell-RNA seq data from two CNON cell lines, one derived from an individual with schizophrenia (SCZ) and the other from a control group, with two biopsy samples from the middle turbinate (MT), also from an individual with SCZ and a control. In addition, we compared our data with previously published data from olfactory neuroepithelium (1). Our data demonstrated that CNON originated from a single cell type which is present both in middle turbinate and olfactory neuroepithelium. CNON express multiple markers of mesenchymal cells. In order to define relatedness of CNON to the developing human brain, we also compared CNON datasets with scRNA-seq data of embryonic brain (2) and found that the expression profile of CNON very closely matched one of the cell types in the embryonic brain. Finally, we evaluated differences between SCZ and control samples to assess usability and potential benefits of using single cell RNA-seq of CNON to study etiology of schizophrenia.

SUBMITTER: Tung VSK

PROVIDER: S-EPMC10081251 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Cultured Mesenchymal Cells from Nasal Turbinate as a Cellular Model of the Neurodevelopmental Component of Schizophrenia Etiology.

Tung Victoria Sook Keng VSK Mathews Fasil F Boruk Marina M Suppa Gabrielle G Foronjy Robert R Pato Michele M Pato Carlos C Knowles James A JA Evgrafov Oleg V OV

bioRxiv : the preprint server for biology 20230329

Study of the neurodevelopmental molecular mechanisms of schizophrenia requires the development of adequate biological models such as patient-derived cells and their derivatives. We previously used cell lines with neural progenitor properties (CNON) derived from superior or middle turbinates of patients with schizophrenia and control groups to study gene expression specific to schizophrenia. In this study, we compared single cell-RNA seq data from two CNON cell lines, one derived from an individu ...[more]

PMID: 37034711

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Project description:The initial events of viral infection at the primary mucosal entry site following horizontal person-to-person transmission have remained ill defined. Our limited understanding is further underscored by the absence of animal models in the case of human-restricted viruses, such as human cytomegalovirus (HCMV), a leading cause of congenital infection and a major pathogen in immunocompromised individuals. Here, we established a novel ex vivo model of HCMV infection in native human nasal turbinate tissues. Nasal turbinate tissue viability and physiological functionality were preserved for at least 7 days in culture. We found that nasal mucosal tissues were susceptible to HCMV infection, with predominant infection of ciliated respiratory epithelial cells. A limited viral spread was demonstrated, involving mainly stromal and vascular endothelial cells within the tissue. Importantly, functional antiviral and proleukocyte chemotactic signaling pathways were significantly upregulated in the nasal mucosa in response to infection. Conversely, HCMV downregulated the expression of nasal epithelial cell-related genes. We further revealed tissue-specific innate immune response patterns to HCMV, comparing infected human nasal mucosal and placental tissues, representing the viral entry and the maternal-to-fetal transmission sites, respectively. Taken together, our studies provide insights into the earliest stages of HCMV infection. Studies in this model could help evaluate new interventions against the horizontal transmission of HCMV.IMPORTANCE HCMV is a ubiquitous human pathogen causing neurodevelopmental disabilities in congenitally infected children and severe disease in immunocompromised patients. The earliest stages of HCMV infection in the human host have remained elusive in the absence of a model for the viral entry site. Here, we describe the establishment and use of a novel nasal turbinate organ culture to study the initial steps of viral infection and the consequent innate immune responses within the natural complexity and the full cellular repertoire of human nasal mucosal tissues. This model can be applied to examine new antiviral interventions against the horizontal transmission of HCMV and potentially that of other viruses.

Project description:BackgroundThe association of the linear dimensions of the inferior turbinate hypertrophy with nasal septal deviation has been studied recently. However, the volumetric dimensions provide a more accurate status of the turbinate hypertrophy compared to linear measurements. The aim of this study was to analyze the association of inferior nasal turbinate volume with the degree of nasal septal deviation (NSD).MethodsA retrospective evaluation of the cone beam computed tomography (CBCT) scans of 412 patients was carried out to obtain 150 scans which were included in the study. The scans were categorized into three groups. Group 1 comprised of 50 scans of patients with no inferior turbinate hypertrophy (ITH) and no nasal septal deviation. Group 2 comprised of 50 scans of patients with ITH and no NSD; whereas Group 3 included 50 scans of patients with ITH and NSD. The total turbinate volume of inferior turbinates (bilateral) were determined by using Vesalius 3D software (PS-Medtech, Amsterdam, Netherlands).ResultsThe intraclass correlation coefficient (ICC) between the volumetric estimations performed by the two radiologists was 0.82. There were no significant age and gender related changes in the total turbinate volume. Patients in Group 3 had significantly higher (p = 0.001) total turbinate volume compared to Group 2 and Group 1. There was a positive and significant correlation (r = 0.52, p = 0.002) between the degree of septal deviation and total turbinate volume. When the total turbinate volume of the patients with different types of septal deviation was compared in Group 3, a statistically significant difference (p = 0.001) was observed. Regression analysis revealed that the septal deviation angle (SDA) (p = 0.001) had a relationship with total turbinate volume. From the results of the study we can conclude that the total turbinate volume is higher in patients with nasal septal deviation. It can also be concluded that the septal deviation angle has a positive correlation with total turbinate volume. The data obtained from the study can be useful in post-surgical follow up and evaluation of patients with nasal septal deviation and hypertrophied inferior nasal turbinate.

Dataset Information

Cultured Mesenchymal Cells from Nasal Turbinate as a Cellular Model of the Neurodevelopmental Component of Schizophrenia Etiology.

Publications

Cultured Mesenchymal Cells from Nasal Turbinate as a Cellular Model of the Neurodevelopmental Component of Schizophrenia Etiology.

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