Differential gene expression between human neurons and neuronal progenitorcells in culture: an analysis of arrayed cDNA clones in NTera2 human embryonal carcinoma cell line as a model system

To elucidate the highly complex expression pattern of the genes involved in human neuronal differentiation, differential gene expression between human neurons and neuronal progenitor cells was investigated by analysis of a cD NA expression array in a pluripotent human embryonal carcinoma cell line NT era2 (NT2), a model system of human neuronal differentiation. Among 588 arr ayed cDNA clones, 87 genes showed a differential expression pattern between undifferentiated neuronal progenitor cells (NT2-U) and NT2-derived differe ntiated neurons induced by treatment with retinoic acid (RA) (NT2-N), while 36 genes could not be analyzed due to high background signals. The levels of expression of 76 genes, including those encoding a group of transcriptio n factors, intracellular signal-transducing proteins, cell death-regulatory proteins, and growth factors/cytokines/neuro-transmitters and their recept ors, were elevated after neuronal differentiation, while the levels of 11 g enes, including those coding for cellular proliferation-related proteins, w ere decreased. Among the differentially expressed genes following induction of neuronal differentiation, significant up-regulation of the growth-assoc iated protein (GAP-43), low-affinity nerve growth factor receptor p75 (LNGF R), and defender against apoptotic cell death (DAD1) mRNAs and substantial down-regulation of the proliferation-associated gene (PAG), fibroblast grow th factor receptor-1 (FGFR-1), and cellular RA-binding protein-II (CRABP-II ) mRNAs were verified by Northern blot analysis. These results indicate tha t the analysis of cDNA expression arrays provides a useful approach for scr eening and identification of a set of distinct genes that undergo highly co mplex regulation during human neuronal differentiation. (C) 2000 Elsevier S cience B.V. All rights reserved.