Physiological genomicsFeb 8, 2007

Daily rhythms of gene activity in fibroblast cells compared with brain clock cells and rat brain clock

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 4, 2026

Abstract

NIH/3T3 fibroblasts showed circadian fluctuations in the expression of 323 functionally diverse transcripts.

Both NIH/3T3 fibroblasts and SCN cells exhibited rhythmic expression of core clock genes such as Per2, Cry1, and Bmal1.
Overlap in rhythmic gene expression was limited to core clock genes and a few others involved in fatty acid and lipid metabolism.
Circadian gene expression in SCN oscillators included a higher prevalence of genes related to glucose metabolism and neurotransmission compared to NIH/3T3 cells.
The inducible form of nitric oxide synthase (iNos) was rhythmically regulated in SCN2.2 cells and the rat SCN, but not in fibroblasts.
Evidence suggests that nitric oxide may play a key role in the pacemaker function of the SCN.

Simplified

To screen for output signals that may distinguish the pacemaker in the mammalian suprachiasmatic nucleus (SCN) from peripheral-type oscillators in which the canonical clockworks are similarly regulated in a circadian manner, the rhythmic behavior of the transcriptome in forskolin-stimulated NIH/3T3 fibroblasts was analyzed and compared relative to SCN2.2 cells in vitro and the rat SCN. Similar to the circadian profiling of the SCN2.2 and rat SCN transcriptomes, NIH/3T3 fibroblasts exhibited circadian fluctuations in the expression of the core clock genes, Per2, Cry1, and Bmal1, and 323 functionally diverse transcripts, many of which regulate cellular communication. Overlap in rhythmic transcripts among NIH/3T3 fibroblasts, SCN2.2 cells, and the rat SCN was limited to these clock genes and four other genes that mediate fatty acid and lipid metabolism or function as nuclear factors. Compared with NIH/3T3 cells, circadian gene expression in SCN oscillators was more prevalent among genes mediating glucose metabolism and neurotransmission. Coupled with evidence for the rhythmic regulation of the inducible isoform of nitric oxide synthase (iNos) in SCN2.2 cells and the rat SCN but not in fibroblasts, studies examining the effects of a NOS inhibitor on metabolic rhythms in cocultures containing SCN2.2 cells and untreated NIH/3T3 cells suggest that the gaseous neurotransmitter nitric oxide may play a key role in SCN pacemaker function. This comparative analysis of circadian gene expression in SCN and non-SCN cells may have important implications in the selective analysis of circadian signals involved in the coupling of SCN oscillators and regulation of rhythmicity in downstream cells.

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Daily rhythms of gene activity in fibroblast cells compared with brain clock cells and rat brain clock

Abstract

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