Gene expression profiling of choline-deprived neural precursor cells isolated from mouse brain.
Choline is an essential nutrient and an important methyl donor. Choline deficiency alters fetal development of the hippocampus in rodents and these changes are associated with decreased memory function lasting throughout life. Also, choline deficiency alters global and gene-specific DNA methylation in several models. This gene expression profiling study describes changes in cortical neural precursor cells from embryonic day 14 mice, after 48 h of exposure to a choline-deficient medium. Using Significance Analysis of Microarrays, we found the expression of 1003 genes to be significantly changed (from a total of 16,000 total genes spotted on the array), with a false discovery rate below 5%. A total of 846 genes were overexpressed while 157 were underexpressed. Classification by gene ontology revealed that 331 of these genes modulate cell proliferation, apoptosis, neuronal and glial differentiation, methyl metabolism, and calcium-binding protein classes. Twenty-seven genes that had changed expression have previously been reported to be regulated by promoter or intron methylation. These findings support our previous work suggesting that choline deficiency decreases the proliferation of neural precursors and possibly increases premature neuronal differentiation and apoptosis.
Niculescu
Mihai D
MD
Department of Nutrition, School of Public Health and School of Medicine, University of North Carolina at Chapel Hill, 2212 McGavran-Greenberg Hall, Chapel Hill, NC 27599-7461, USA.
Craciunescu
Corneliu N
CN
Zeisel
Steven H
SH
D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D002796:Choline Deficiency / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian; D015870:Gene Expression / Q000502:physiology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013234:Stem Cells / Q000502:physiology*
D012333:RNA, Messenger