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

Evgrafov, Oleg V.a; Wrobel, Bozena B.b; Kang, Xina; Simpson, Georgea; Malaspina, Doloresc; Knowles, James A.a

doi: 10.1097/YPG.0b013e328341a2f0
Original Articles

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.

aDepartments of Psychiatry and Behavioral Sciences

bOtolaryngology, University of Southern California, Los Angeles, California

cDepartment of Psychiatry, New York University, New York, USA

Correspondence to Oleg V. Evgrafov, PhD, Department of Psychiatry and Behavioral Sciences, University of Southern California, 1501 San Pablo Street, ZNI 401, Los Angeles, CA 90089-2821, USA Tel: +1 323 442 1927; fax: +1 323 442 2448; e-mail: evgrafov@keck.usc.edu

Received September 11, 2009

Accepted June 29, 2010

© 2011 Lippincott Williams & Wilkins, Inc.