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Circadian rhythms of fetal liver transcription persist in the absence of canonical circadian clock gene expression rhythms in vivo.

Li C, Yu S, Zhong X, Wu J, Li X - PLoS ONE (2012)

Bottom Line: In the fetal liver we did not observe circadian rhythms of clock gene expression or many other transcripts known to be rhythmically expressed in the adult liver.Upon data filtering by coefficient of variation, the expression levels for transcripts related to pancreatic exocrine enzymes and zymogen secretion were found to undergo synchronized daily fluctuations at high amplitudes.These results suggest that maternal cues influence the fetal liver, despite the fact that we did not detect circadian rhythms of canonical clock gene expression in the fetal liver.

View Article: PubMed Central - PubMed

Affiliation: National Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei Province, People's Republic of China.

ABSTRACT
The cellular circadian clock and systemic cues drive rhythmicity in the transcriptome of adult peripheral tissues. However, the oscillating status of the circadian clocks in fetal tissues, and their response to maternal cues, are less clear. Most clock genes do not cycle in fetal livers from mice and rats, although tissue level rhythms rapidly emerge when fetal mouse liver explants are cultured in vitro. Thus, in the fetal mouse liver, the circadian clock does not oscillate at the cellular level (but is induced to oscillate in culture). To gain a comprehensive overview of the clock status in the fetal liver during late gestation, we performed microarray analyses on fetal liver tissues. In the fetal liver we did not observe circadian rhythms of clock gene expression or many other transcripts known to be rhythmically expressed in the adult liver. Nevertheless, JTK_CYCLE analysis identified some transcripts in the fetal liver that were rhythmically expressed, albeit at low amplitudes. Upon data filtering by coefficient of variation, the expression levels for transcripts related to pancreatic exocrine enzymes and zymogen secretion were found to undergo synchronized daily fluctuations at high amplitudes. These results suggest that maternal cues influence the fetal liver, despite the fact that we did not detect circadian rhythms of canonical clock gene expression in the fetal liver. These results raise important questions on the role of the circadian clock, or lack thereof, during ontogeny.

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Heatmap of 66 probe sets representing clock and known rhythmic genes.Natural scale expression values from series 2 data for core clock genes and genes known to be rhythmically expressed in the adult liver were plotted with Heatmap builder. Some genes were represented by multiple probe sets. Phases were sorted by the “lag” values given by JTK_CYCLE.
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pone-0030781-g001: Heatmap of 66 probe sets representing clock and known rhythmic genes.Natural scale expression values from series 2 data for core clock genes and genes known to be rhythmically expressed in the adult liver were plotted with Heatmap builder. Some genes were represented by multiple probe sets. Phases were sorted by the “lag” values given by JTK_CYCLE.

Mentions: A previous quantitative RT-PCR study of fetal mouse liver had failed to detect circadian rhythms of clock gene expression [21]. Consistent with this, our JTK_CYCLE [23] analyses of GC-RMA [24] normalized fetal liver expression values on embryonic day (E)18 and E19 indicated that nearly all the known clock genes did not show circadian rhythms of expression in the fetal liver, including BMAL1/Arntl, BMAL2/Arntl2, CLOCK, Cry1, Cry2, Csnk1d, Csnk1e, Fbxl3, Npas2, Per1, Per2, Per3, Rora, Rorb, Rorc, Rev-erb α/NR1D1, and Rev-erb β/NR1D2 (Table S1). Many genes known to be rhythmically expressed in the adult mouse liver also did not show circadian rhythms of expression, such as Alas1 (Delta-aminolevulinate synthase 1), Ces3 (carboxylesterase 3), Cyp7a1 (cytochrome P450 7a-hydroxylase), Cyp2b10, Dbp, Gck (glucose kinase), Slc2a2/GluT2, Gys2 (glycogen synthase 2), Hlf (hepatic leukemia factor), Lpin1 (lipin-1), Nampt (nicotinamide phosphoribosyltransferase), Pck1 (phosphoenolpyruvate carboxykinase 1), Por (cytochrome P450 oxidoreducatase), Tef (thyrotroph embryonic factor) and Wee1[7], [25], [26], [27], [28]. Overall, we evaluated 66 probe sets representing clock genes and known rhythmic transcripts in the adult liver (Figures 1 and S1; Table S1). Few rhythmic transcripts were identified in either of our two data series by JTK_CYCLE analysis, and none were common to both data series. Furthermore, most transcripts showed peak to trough variations of less than 2.5 fold over the two days of late gestation. Taken together, our results strengthened the view that circadian regulatory cycles are not present in the fetal mouse liver at the tissue level.


Circadian rhythms of fetal liver transcription persist in the absence of canonical circadian clock gene expression rhythms in vivo.

Li C, Yu S, Zhong X, Wu J, Li X - PLoS ONE (2012)

Heatmap of 66 probe sets representing clock and known rhythmic genes.Natural scale expression values from series 2 data for core clock genes and genes known to be rhythmically expressed in the adult liver were plotted with Heatmap builder. Some genes were represented by multiple probe sets. Phases were sorted by the “lag” values given by JTK_CYCLE.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3285613&req=5

pone-0030781-g001: Heatmap of 66 probe sets representing clock and known rhythmic genes.Natural scale expression values from series 2 data for core clock genes and genes known to be rhythmically expressed in the adult liver were plotted with Heatmap builder. Some genes were represented by multiple probe sets. Phases were sorted by the “lag” values given by JTK_CYCLE.
Mentions: A previous quantitative RT-PCR study of fetal mouse liver had failed to detect circadian rhythms of clock gene expression [21]. Consistent with this, our JTK_CYCLE [23] analyses of GC-RMA [24] normalized fetal liver expression values on embryonic day (E)18 and E19 indicated that nearly all the known clock genes did not show circadian rhythms of expression in the fetal liver, including BMAL1/Arntl, BMAL2/Arntl2, CLOCK, Cry1, Cry2, Csnk1d, Csnk1e, Fbxl3, Npas2, Per1, Per2, Per3, Rora, Rorb, Rorc, Rev-erb α/NR1D1, and Rev-erb β/NR1D2 (Table S1). Many genes known to be rhythmically expressed in the adult mouse liver also did not show circadian rhythms of expression, such as Alas1 (Delta-aminolevulinate synthase 1), Ces3 (carboxylesterase 3), Cyp7a1 (cytochrome P450 7a-hydroxylase), Cyp2b10, Dbp, Gck (glucose kinase), Slc2a2/GluT2, Gys2 (glycogen synthase 2), Hlf (hepatic leukemia factor), Lpin1 (lipin-1), Nampt (nicotinamide phosphoribosyltransferase), Pck1 (phosphoenolpyruvate carboxykinase 1), Por (cytochrome P450 oxidoreducatase), Tef (thyrotroph embryonic factor) and Wee1[7], [25], [26], [27], [28]. Overall, we evaluated 66 probe sets representing clock genes and known rhythmic transcripts in the adult liver (Figures 1 and S1; Table S1). Few rhythmic transcripts were identified in either of our two data series by JTK_CYCLE analysis, and none were common to both data series. Furthermore, most transcripts showed peak to trough variations of less than 2.5 fold over the two days of late gestation. Taken together, our results strengthened the view that circadian regulatory cycles are not present in the fetal mouse liver at the tissue level.

Bottom Line: In the fetal liver we did not observe circadian rhythms of clock gene expression or many other transcripts known to be rhythmically expressed in the adult liver.Upon data filtering by coefficient of variation, the expression levels for transcripts related to pancreatic exocrine enzymes and zymogen secretion were found to undergo synchronized daily fluctuations at high amplitudes.These results suggest that maternal cues influence the fetal liver, despite the fact that we did not detect circadian rhythms of canonical clock gene expression in the fetal liver.

View Article: PubMed Central - PubMed

Affiliation: National Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei Province, People's Republic of China.

ABSTRACT
The cellular circadian clock and systemic cues drive rhythmicity in the transcriptome of adult peripheral tissues. However, the oscillating status of the circadian clocks in fetal tissues, and their response to maternal cues, are less clear. Most clock genes do not cycle in fetal livers from mice and rats, although tissue level rhythms rapidly emerge when fetal mouse liver explants are cultured in vitro. Thus, in the fetal mouse liver, the circadian clock does not oscillate at the cellular level (but is induced to oscillate in culture). To gain a comprehensive overview of the clock status in the fetal liver during late gestation, we performed microarray analyses on fetal liver tissues. In the fetal liver we did not observe circadian rhythms of clock gene expression or many other transcripts known to be rhythmically expressed in the adult liver. Nevertheless, JTK_CYCLE analysis identified some transcripts in the fetal liver that were rhythmically expressed, albeit at low amplitudes. Upon data filtering by coefficient of variation, the expression levels for transcripts related to pancreatic exocrine enzymes and zymogen secretion were found to undergo synchronized daily fluctuations at high amplitudes. These results suggest that maternal cues influence the fetal liver, despite the fact that we did not detect circadian rhythms of canonical clock gene expression in the fetal liver. These results raise important questions on the role of the circadian clock, or lack thereof, during ontogeny.

Show MeSH
Related in: MedlinePlus