Boruk, M. | bioRxiv Science

bioRxiv2023

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

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.

cell biology↗

bioRxiv2022

Cell type catalog of middle turbinate epithelium

ImportanceElucidation of the cellular makeup of the middle turbinate provides a foundation for future studies of pathogenesis of sinonasal disease. Neural progenitors and pluripotent basal cells found in middle turbinate mucosa potentially can be used to develop cellular models to study brain disorders or in regenerative medicine to substitute neuronal tissues. ObjectiveSingle cell RNA-sequencing (scRNA-seq) of middle turbinate mucosa was performed to create the first single cell transcriptome catalog of this part of the human body. DesignSamples were obtained from the head of the middle turbinate from healthy volunteers. After the specimen was prepared per lab protocol, cells were dissociated, suspended, and counted. Single cell libraries were then prepared according to the 10x Genomics protocol and sequenced using NovaSeq 6000 (Illumina). Sequencing data were processed using Cell Ranger, and clustering and gene expression analysis was performed using Seurat. Cell types were annotated using known markers and data from other single cell studies. SettingSingle center, tertiary care center ParticipantsHealthy volunteer Intervention(s) (for clinical trials) or Exposure(s) (for observational studies)None Main Outcome(s) and Measure(s)Identification of cell types of middle turbinate mucosa through expression profiling of single cells using known markers Results14 unique cell types were identified, including serous, goblet, club, basal, ciliated, endothelial, and neural progenitor cells, as well as multiple types of blood cells. Conclusions and RelevanceThis catalog provides a comprehensive depiction of the cellular composition of middle turbinate mucosa. By uncovering the cellular stratification of gene expression profiles in healthy middle turbinate epithelium, the groundwork has been laid for further investigation into the molecular pathogenesis and targeted therapy of sinonasal disease. Key PointsO_ST_ABSQuestionC_ST_ABSWhat is the cellular makeup of human middle turbinate mucosa? FindingsSingle-cell RNA sequencing revealed 14 cell types in middle turbinate epithelium, including neural progenitors, a previously unrecognized component of middle turbinate epithelium. MeaningGene expression profiles of middle turbinate mucosa cell types are concordant with other respiratory mucosa transcriptomic data with notable heterogeneity in serous and basal cells.{square}

genomics↗