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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 the 145 rhythmic probe sets in series 2 microarray data.Series 2 natural scale expression values for the 145 probe sets that were rhythmic in both series of data (p<0.1 by JTK_CYCLE) were plotted. Phases were sorted by the “lag” values given by JTK_CYCLE.
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pone-0030781-g002: Heatmap of the 145 rhythmic probe sets in series 2 microarray data.Series 2 natural scale expression values for the 145 probe sets that were rhythmic in both series of data (p<0.1 by JTK_CYCLE) were plotted. Phases were sorted by the “lag” values given by JTK_CYCLE.

Mentions: Despite the failure to detect circadian rhythms in fetal liver for the set of transcripts known to have robust expression rhythms in the adult liver, JTK_CYCLE analysis revealed many rhythmic transcripts (criteria: p<0.1) in each of our data series. However, the p-values after corrections for multiple measurements were rather high (BH.Q values>0.4), suggesting that these genes were less likely to be truly rhythmic. Furthermore, the amplitudes of the expression rhythms were generally low for those rhythmic transcripts, with most probe sets showing less than 2.5-fold changes between expression peaks and troughs for the 12 time points examined. Nonetheless, a common set of 145 probe sets was found to be rhythmic in both series of data (Figures 2 and S2; Table S2). DAVID analyses [29] on those common rhythmic transcripts revealed significant enrichments for genes involved in mitochondrial function (Table S3). Those transcripts included: Dlat (dihydrolipoamide S-acetyltransferase, the E2 compoment of the pyruvate dehydrogenase complex linking glycolysis to TCA cycle), Cs (citrate synthase in TCA cycle), and Cox18 (cytochrome c oxidase assembly protein 18). Three genes in the glycolysis/gluconeogenesis pathway (Pgk1 (phosphoglycerate kinase 1), Pgam1 (phosphoglycerate mutase 1) and Tpi1 (triosephosphate isomerase 1) were also enriched (with uncorrected p-value at 0.0036 and Benjamini corrected p-value at 0.085, approaching significance). Of those 145 probe sets, 58 (including Pgk1, Pgam1, Tpi1, Dlat, Cs and Cox18) were also rhythmic in adult mouse liver (BH.Q<0.1 in GSE11923 [30]; Table S2). In addition, IRS2 (insulin receptor substrate 2) was also found to be rhythmically expressed in both fetal and adult livers (Table S2).


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 the 145 rhythmic probe sets in series 2 microarray data.Series 2 natural scale expression values for the 145 probe sets that were rhythmic in both series of data (p<0.1 by JTK_CYCLE) were plotted. 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-g002: Heatmap of the 145 rhythmic probe sets in series 2 microarray data.Series 2 natural scale expression values for the 145 probe sets that were rhythmic in both series of data (p<0.1 by JTK_CYCLE) were plotted. Phases were sorted by the “lag” values given by JTK_CYCLE.
Mentions: Despite the failure to detect circadian rhythms in fetal liver for the set of transcripts known to have robust expression rhythms in the adult liver, JTK_CYCLE analysis revealed many rhythmic transcripts (criteria: p<0.1) in each of our data series. However, the p-values after corrections for multiple measurements were rather high (BH.Q values>0.4), suggesting that these genes were less likely to be truly rhythmic. Furthermore, the amplitudes of the expression rhythms were generally low for those rhythmic transcripts, with most probe sets showing less than 2.5-fold changes between expression peaks and troughs for the 12 time points examined. Nonetheless, a common set of 145 probe sets was found to be rhythmic in both series of data (Figures 2 and S2; Table S2). DAVID analyses [29] on those common rhythmic transcripts revealed significant enrichments for genes involved in mitochondrial function (Table S3). Those transcripts included: Dlat (dihydrolipoamide S-acetyltransferase, the E2 compoment of the pyruvate dehydrogenase complex linking glycolysis to TCA cycle), Cs (citrate synthase in TCA cycle), and Cox18 (cytochrome c oxidase assembly protein 18). Three genes in the glycolysis/gluconeogenesis pathway (Pgk1 (phosphoglycerate kinase 1), Pgam1 (phosphoglycerate mutase 1) and Tpi1 (triosephosphate isomerase 1) were also enriched (with uncorrected p-value at 0.0036 and Benjamini corrected p-value at 0.085, approaching significance). Of those 145 probe sets, 58 (including Pgk1, Pgam1, Tpi1, Dlat, Cs and Cox18) were also rhythmic in adult mouse liver (BH.Q<0.1 in GSE11923 [30]; Table S2). In addition, IRS2 (insulin receptor substrate 2) was also found to be rhythmically expressed in both fetal and adult livers (Table S2).

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