Microarray Database Mining and Cell Differentiation Defects in Schizophrenia
The causes of schizophrenia remain unknown, but a key role of oligodendrocytes and of the myelination process carried out by them has gained increasing support. The adult human brain parenchyma contains a relatively large population of progenitor cells that can generate oligodendrocytes. Defects in these adult oligodendrocyte progenitor cells (OPCs) or in their proliferation/differentiation have received little attention as potential causes of schizophrenia yet. We compared the set of genes whose expression is modified in schizophrenia, as revealed by our microarray studies, with genes specifically expressed in stem cells, as revealed by studies on human embryonic stem cells. We also evaluated the genes that are upregulated when stem cells engage in differentiation programs. These genes can be viewed as fingerprints or signatures for differentiation processes. The comparisons revealed that a substantial fraction of the genes downregulated in the brains of persons with schizophrenia belong to the differentiation signature. A plausible interpretation of our observations is that a cell differentiation process, possibly of adult OPCs to oligodendrocytes, is perturbed in schizophrenia. These observations constitute an incentive for a new direction of study, aimed at investigating the potential role of OPCs in schizophrenia.
KeywordsNeural Progenitor Cell Subventricular Zone Human ESCs Oligodendrocyte Progenitor Cell Superior Temporal Cortex
We thank Drs Mayte Suárez-Fariñas and Marcelo Magnasco from the Rockefeller University for sharing data, critical reading of the manuscript, and evaluation of the computational/statistical aspects, and Dr Gregory Elder from the Mount Sinai School of Medicine for suggestions and comments. This research was funded by MH45212 (KLD), MH064673 and VA-MIRECC (VH). The generation of the microarray data used here was supported in part by research sponsored by Gene Logic Inc. (Gaithersburg, MD).