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.

Editorial: Olfactory neuroepithelium-derived cellular models to study neurological and psychiatric disorders

“…This team presented their new study in this special topic, describing a protocol for an efficient manufacturing process for clinical-grade olfactory stem cells, which could be used to promote the recovery of spinal cord trauma, hearing loss, Parkinson's disease, amnesia, and peripheral nerve injury (Jaloux et al). Mesenchymal cells derived from the respiratory epithelium of the middle or superior turbinates are very similar to the cells in the embryonic brain (Tung et al, 2023), further supporting the idea of the important role of mesenchymal cells in brain disorders.…”

“…Studies of the ON as a model system of brain development and neurodegeneration have shown impressive evolution, accommodating new technologies, such as epigenetic methodologies (Rhie et al, 2018) and single-cell transcriptomics (Oliva et al, 2022;Tung et al, 2023), and they are growing in scale (Evgrafov et al, 2020). This topic demonstrates increased diversity and new dimensionalities, widening the borders of cell models to use them for drug discovery (Mihaljevic et al) and for cell therapy (Jaloux et al) as well as continuing the addition of conditions that could be modeled by cells from the ON (Fang et al).…”

“…This topic demonstrates increased diversity and new dimensionalities, widening the borders of cell models to use them for drug discovery (Mihaljevic et al) and for cell therapy (Jaloux et al) as well as continuing the addition of conditions that could be modeled by cells from the ON (Fang et al). These studies are based on our improved understanding of the relationships between the ON and the brain (Palominos et al; Tung et al, 2023).…”

Cell Type Catalog of Middle Turbinate Epithelium (Cell Catalog of Turbinate Epithelium)

“…Previously we used superior turbinate and middle turbinate biopsies to produce cell lines with neural progenitor characteristics (CNON), 53 and we identified in this study mesenchymal cells as a cell type with an expression profile very close to CNON (expressing ACTA2, MAP1B , and COL1A2) thus being likely a precursor of CNON ( Figure 5 ). 54 Endothelial cells were characterized by expression of ACKR1 , SELE , SOX18, MME , EDN1 , PLVAP , and VWF ( Figure 6 ). 55 …”