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Sex hormones have pervasive effects on thymic epithelial cells.

Dumont-Lagacé M, St-Pierre C, Perreault C - Sci Rep (2015)

Bottom Line: These effects were exquisitely TEC-subset specific.Nevertheless, cTECs were more abundant in males than females.Accumulation of cTECs in males correlated with differential expression of genes regulating cell survival in cTECs and cell differentiation in mTECs.

View Article: PubMed Central - PubMed

Affiliation: 1] Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, QC, Canada H3C 3J7 [2] Department of Medicine, Université de Montréal, Montreal, QC, Canada H3C 3J7.

ABSTRACT
The goal of our study was to evaluate at the systems-level, the effect of sex hormones on thymic epithelial cells (TECs). To this end, we sequenced the transcriptome of cortical and medullary TECs (cTECs and mTECs) from three groups of 6 month-old mice: males, females and males castrated at four weeks of age. In parallel, we analyzed variations in the size of TEC subsets in those three groups between 1 and 12 months of age. We report that sex hormones have pervasive effects on the transcriptome of TECs. These effects were exquisitely TEC-subset specific. Sexual dimorphism was particularly conspicuous in cTECs. Male cTECs displayed low proliferation rates that correlated with low expression of Foxn1 and its main targets. Furthermore, male cTECs expressed relatively low levels of genes instrumental in thymocyte expansion (e.g., Dll4) and positive selection (Psmb11 and Ctsl). Nevertheless, cTECs were more abundant in males than females. Accumulation of cTECs in males correlated with differential expression of genes regulating cell survival in cTECs and cell differentiation in mTECs. The sexual dimorphism of TECs highlighted here may be mechanistically linked to the well-recognized sex differences in susceptibility to infections and autoimmune diseases.

No MeSH data available.


Related in: MedlinePlus

IPA analysis of DEGs in cTECs and mTECs.IPA analysis of DEGs predicts decreased cell death and cell differentiation in males. Activation Z-scores are depicted with bars, whereas p values are shown with black dots. The color of bars shows in which group a given process is activated (e.g., blue = males). All functions represented on the graph were significantly enriched (p < 0.05).
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f3: IPA analysis of DEGs in cTECs and mTECs.IPA analysis of DEGs predicts decreased cell death and cell differentiation in males. Activation Z-scores are depicted with bars, whereas p values are shown with black dots. The color of bars shows in which group a given process is activated (e.g., blue = males). All functions represented on the graph were significantly enriched (p < 0.05).

Mentions: To better understand of the impact of sex hormones on TEC function, we performed a downstream effect analysis on our lists of DEGs using the Ingenuity Pathway Analysis software (IPA, Ingenuity® Systems, www.ingenuity.com). We used two metrics to identify the most important downstream effects of these DEGs: activation Z-score and p-value. Positive and negative Z-scores indicate increased and decreased functional activity, respectively. The p-value, calculated with the Fischer’s exact test, indicates the likelihood that the association between a set of DEGs and a biological function is significant. The complete list of biological processes regulated by DEGs can be found in Supplementary Figures S2 and S3. Of particular relevance in view of differences in TEC subsets depicted in Fig. 1, the following functional categories were highlighted as being differentially activated in the three experimental groups: cell death and survival and cell differentiation (Fig. 3). More specifically, IPA analysis predicted that, relative to the two other groups, male TECs would show i) less cell death (cTECs and mTECs) and ii) less cell differentiation (mTECs). Superior cTEC survival coupled to lessened differentiation of cTEC-phenotype progenitors into mTECs offer a plausible explanation for the higher numbers of cTECs observed in males (Fig. 1a).


Sex hormones have pervasive effects on thymic epithelial cells.

Dumont-Lagacé M, St-Pierre C, Perreault C - Sci Rep (2015)

IPA analysis of DEGs in cTECs and mTECs.IPA analysis of DEGs predicts decreased cell death and cell differentiation in males. Activation Z-scores are depicted with bars, whereas p values are shown with black dots. The color of bars shows in which group a given process is activated (e.g., blue = males). All functions represented on the graph were significantly enriched (p < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4528223&req=5

f3: IPA analysis of DEGs in cTECs and mTECs.IPA analysis of DEGs predicts decreased cell death and cell differentiation in males. Activation Z-scores are depicted with bars, whereas p values are shown with black dots. The color of bars shows in which group a given process is activated (e.g., blue = males). All functions represented on the graph were significantly enriched (p < 0.05).
Mentions: To better understand of the impact of sex hormones on TEC function, we performed a downstream effect analysis on our lists of DEGs using the Ingenuity Pathway Analysis software (IPA, Ingenuity® Systems, www.ingenuity.com). We used two metrics to identify the most important downstream effects of these DEGs: activation Z-score and p-value. Positive and negative Z-scores indicate increased and decreased functional activity, respectively. The p-value, calculated with the Fischer’s exact test, indicates the likelihood that the association between a set of DEGs and a biological function is significant. The complete list of biological processes regulated by DEGs can be found in Supplementary Figures S2 and S3. Of particular relevance in view of differences in TEC subsets depicted in Fig. 1, the following functional categories were highlighted as being differentially activated in the three experimental groups: cell death and survival and cell differentiation (Fig. 3). More specifically, IPA analysis predicted that, relative to the two other groups, male TECs would show i) less cell death (cTECs and mTECs) and ii) less cell differentiation (mTECs). Superior cTEC survival coupled to lessened differentiation of cTEC-phenotype progenitors into mTECs offer a plausible explanation for the higher numbers of cTECs observed in males (Fig. 1a).

Bottom Line: These effects were exquisitely TEC-subset specific.Nevertheless, cTECs were more abundant in males than females.Accumulation of cTECs in males correlated with differential expression of genes regulating cell survival in cTECs and cell differentiation in mTECs.

View Article: PubMed Central - PubMed

Affiliation: 1] Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, QC, Canada H3C 3J7 [2] Department of Medicine, Université de Montréal, Montreal, QC, Canada H3C 3J7.

ABSTRACT
The goal of our study was to evaluate at the systems-level, the effect of sex hormones on thymic epithelial cells (TECs). To this end, we sequenced the transcriptome of cortical and medullary TECs (cTECs and mTECs) from three groups of 6 month-old mice: males, females and males castrated at four weeks of age. In parallel, we analyzed variations in the size of TEC subsets in those three groups between 1 and 12 months of age. We report that sex hormones have pervasive effects on the transcriptome of TECs. These effects were exquisitely TEC-subset specific. Sexual dimorphism was particularly conspicuous in cTECs. Male cTECs displayed low proliferation rates that correlated with low expression of Foxn1 and its main targets. Furthermore, male cTECs expressed relatively low levels of genes instrumental in thymocyte expansion (e.g., Dll4) and positive selection (Psmb11 and Ctsl). Nevertheless, cTECs were more abundant in males than females. Accumulation of cTECs in males correlated with differential expression of genes regulating cell survival in cTECs and cell differentiation in mTECs. The sexual dimorphism of TECs highlighted here may be mechanistically linked to the well-recognized sex differences in susceptibility to infections and autoimmune diseases.

No MeSH data available.


Related in: MedlinePlus