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

Abstract

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

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…”