Olfactory neuroepithelium-derived neural progenitor cells as a model system for investigating the molecular mechanisms of neuropsychiatric disorders

Objective Most expression profiling studies of neuropsychiatric disorders have used RNA from postmortem brain tissue. Such studies are confounded by terminal events, environmental variables, such as drug use or abuse, postmortem interval, and tissue pH. To address these limitations, we have explored the use of cultured neuronal cells derived from olfactory neuroepithelium (CNON) from nasal biopsies as an alternate source of RNA. CNON cells are primarily composed of neural progenitor cells and are less influenced by environmental variables as compared with adult postmortem brain tissue. Methods We collected biopsy samples and established CNON cultures from eight schizophrenia cases and eight healthy comparison individuals. RNA from the cells was profiled using Affymetrix Human Exon 1.0 ST arrays and the results were validated by immunostaining and real-time quantitative PCR. Results The expression data show that CNON are primarily composed of neural progenitor cells. Furthermore, we observed a substantially higher correlation of global expression between control samples of CNON (0.98), as compared with postmortem tissue (GDS1917) (0.88). Finally, using the genome-wide expression data, we were able to differentiate CNON samples derived from individuals with and without schizophrenia in a principal component analysis and to identify candidate schizophrenia genes. Conclusion CNON is a novel model system for the study of neuropsychiatric disorders that drastically reduces both technical and biological noise as compared with postmortem tissue and is therefore well suited for the identification of genes that are differentially expressed between cases and controls. Psychiatr Genet 21:217-228 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.