Differential gene expression between human neurons and neuronal progenitor cells 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 cDNA expression array in a pluripotent human embryonal carcinoma cell line NTera2 (NT2), a model system of human neuronal differentiation. Among 588 arrayed cDNA clones, 87 genes showed a differential expression pattern between undifferentiated neuronal progenitor cells (NT2-U) and NT2-derived differentiated neurons induced by treatment with retinoic acid (RA) (NT2-N), while 26 genes could not be analyzed due to high background signals. The levels of expression of 76 genes, including those encoding a group of transcription factors, intracellular signal-transducing proteins, cell death-regulatory proteins, and growth factors/cytokines/neurotransmitters and their receptors, were elevated after neuronal differentiation, while the levels of 11 genes, including those coding for cellular proliferation-related proteins, were decreased. Among the differentially expressed genes following induction of neuronal differentiation, significant up-regulation of the growth-associated protein (GAP-43), low-affinity nerve growth factor receptor p75 (LNGFR), and defender against apoptotic cell death (DAD1) mRNAs and substantial down-regulation of the proliferation-associated gene (PAG), fibroblast growth factor receptor-1 (FGFR-1), and cellular RA-binding protein-II (CRABP-II) mRNAs were verified by Northern blot analysis. These results indicate that the analysis of cDNA expression arrays provides a useful approach for screening and identification of a set of distinct genes that undergo highly complex regulation during human neuronal differentiation.