Affiliations: Cellular Neurobiology Research Branch, Intramural
Research Program, National Institute on Drug Abuse, National Institutes of
Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA | DNA Array Unit, National Institute on Aging, National
Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA | University of California, Irvine, Psychiatry &
Human Behavior, Irvine, CA 92697, USA
Abstract: Purpose: The human SH-SY5Y cell line is an established model for
retinoic acid (RA)-induced neural differentiation. We employed a broad human
15K microarray (15,000 genes) and focused Neuroarray (1152 genes) to examine
changes in gene expression early in the process of differentiation (6 hr),
before morphology or growth changes are observed. Methods: 33 P-labeled CDNA
probes prepared from RNA extracts of RA-treated and control cultures were
hybridized to array membranes, and levels of expression were quantified and
compared. Results: In the 15K array, 19 % of the genes were decreased (0.4 %
were named genes and the remainder were expressed sequence tags (ESTs) or
unknowns), and 9 % were increased (4.2 % named genes). In the Neuroarray, 3 %
were decreased and 8 % were inereased. Conclusions: Summary gene profiles are
presented, which include transcription factors, genes associated with cell
cycle, cell shape, neurotransmission, intermediary filaments, and others. The
prevalence of down-regulated genes in the broad 15K array and up-regulated
genes in the neuro-focused array suggests a pattem shift in gene expression
associated with differentiation. The predominance of ESTs among the
down-regulated genes indicates a great number of as-yet-unidentified genes are
repressed in early stage neural differentiation.
