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Comparison of the Transcriptional Profiles of Melanocytes from Dark and Light Skinned Individuals under Basal Conditions and Following Ultraviolet-B Irradiation.

López S, Smith-Zubiaga I, García de Galdeano A, Boyano MD, García O, Gardeazábal J, Martinez-Cadenas C, Izagirre N, de la Rúa C, Alonso S - PLoS ONE (2015)

Bottom Line: Our results suggest that an interaction between ribosomal proteins and the P53 signaling pathway may occur in response to UVB in both DM and LM.Furthermore, the culture with KCM+ compared with KCM- had a noticeable effect on LM.This effect includes the activation of various signaling pathways such as the mTOR pathway, involved in the regulation of cell metabolism, growth, proliferation and survival.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Physical Anthropology and Animal Physiology. University of the Basque Country UPV/EHU, Leioa, Bizkaia, Spain.

ABSTRACT
We analysed the whole-genome transcriptional profile of 6 cell lines of dark melanocytes (DM) and 6 of light melanocytes (LM) at basal conditions and after ultraviolet-B (UVB) radiation at different time points to investigate the mechanisms by which melanocytes protect human skin from the damaging effects of UVB. Further, we assessed the effect of different keratinocyte-conditioned media (KCM+ and KCM-) on melanocytes. Our results suggest that an interaction between ribosomal proteins and the P53 signaling pathway may occur in response to UVB in both DM and LM. We also observed that DM and LM show differentially expressed genes after irradiation, in particular at the first 6h after UVB. These are mainly associated with inflammatory reactions, cell survival or melanoma. Furthermore, the culture with KCM+ compared with KCM- had a noticeable effect on LM. This effect includes the activation of various signaling pathways such as the mTOR pathway, involved in the regulation of cell metabolism, growth, proliferation and survival. Finally, the comparison of the transcriptional profiles between LM and DM under basal conditions, and the application of natural selection tests in human populations allowed us to support the significant evolutionary role of MIF and ATP6V0B in the pigmentary phenotype.

No MeSH data available.


Related in: MedlinePlus

Principal Component Analysis.Charts a) and b) show the same 2-dimesional representation of the data according to the first 2 principal components, but colored according to different variables. Thus, in a) the effects of time (Squares: Time = 0; Dots: Time = 6 hours; Triangles: Time = 12 hours; Diamonds: Time = 24 hours) and pigmentation (Yellow = Light melanocytes; Brown = Dark melanocytes) are highlighted, while in b), it is the time (Squares: Time = 0; Dots: Time = 6 hours; Triangles: Time = 12 hours; Diamonds: Time = 24 hours) and the type of KCM used which are highlighted (Green: KCM-; Red: KCM+).
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pone.0134911.g002: Principal Component Analysis.Charts a) and b) show the same 2-dimesional representation of the data according to the first 2 principal components, but colored according to different variables. Thus, in a) the effects of time (Squares: Time = 0; Dots: Time = 6 hours; Triangles: Time = 12 hours; Diamonds: Time = 24 hours) and pigmentation (Yellow = Light melanocytes; Brown = Dark melanocytes) are highlighted, while in b), it is the time (Squares: Time = 0; Dots: Time = 6 hours; Triangles: Time = 12 hours; Diamonds: Time = 24 hours) and the type of KCM used which are highlighted (Green: KCM-; Red: KCM+).

Mentions: Second, we performed a Principal Component Analysis (PCA), an exploratory multivariate statistical technique for simplifying complex data sets [30], that has been used for the analysis of microarray data in search of outlier genes [31] or to identify temporal patterns in time-series analyses [32]. The PCA (Fig 2) allowed us to have an overview of the temporal patterns or differentially expressed genes between dark and light melanocytes, or between the culture with KCM+ or KCM-. It showed an apparent general homogeneity, revealing no additional potential outliers and a coherent clustering of our samples according to different variables, which was valuable to discard the presence of outliers or experimental errors. The PCA showed a time-point clustering defined by the second component, revealing a major separation of the samples at 6 hours, while the samples corresponding to 12 and 24 hours clustered close to the controls (0 hours), thus suggesting an early response from melanocytes to UVB that returned again to basal levels after the first 6 hours. At 6 hours we also observed a differential response according to pigmentation defined by the first component. At 24 hours, an apparent clustering regarding the culture of light melanocytes with KCM- or KCM+ was also noticed.


Comparison of the Transcriptional Profiles of Melanocytes from Dark and Light Skinned Individuals under Basal Conditions and Following Ultraviolet-B Irradiation.

López S, Smith-Zubiaga I, García de Galdeano A, Boyano MD, García O, Gardeazábal J, Martinez-Cadenas C, Izagirre N, de la Rúa C, Alonso S - PLoS ONE (2015)

Principal Component Analysis.Charts a) and b) show the same 2-dimesional representation of the data according to the first 2 principal components, but colored according to different variables. Thus, in a) the effects of time (Squares: Time = 0; Dots: Time = 6 hours; Triangles: Time = 12 hours; Diamonds: Time = 24 hours) and pigmentation (Yellow = Light melanocytes; Brown = Dark melanocytes) are highlighted, while in b), it is the time (Squares: Time = 0; Dots: Time = 6 hours; Triangles: Time = 12 hours; Diamonds: Time = 24 hours) and the type of KCM used which are highlighted (Green: KCM-; Red: KCM+).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526690&req=5

pone.0134911.g002: Principal Component Analysis.Charts a) and b) show the same 2-dimesional representation of the data according to the first 2 principal components, but colored according to different variables. Thus, in a) the effects of time (Squares: Time = 0; Dots: Time = 6 hours; Triangles: Time = 12 hours; Diamonds: Time = 24 hours) and pigmentation (Yellow = Light melanocytes; Brown = Dark melanocytes) are highlighted, while in b), it is the time (Squares: Time = 0; Dots: Time = 6 hours; Triangles: Time = 12 hours; Diamonds: Time = 24 hours) and the type of KCM used which are highlighted (Green: KCM-; Red: KCM+).
Mentions: Second, we performed a Principal Component Analysis (PCA), an exploratory multivariate statistical technique for simplifying complex data sets [30], that has been used for the analysis of microarray data in search of outlier genes [31] or to identify temporal patterns in time-series analyses [32]. The PCA (Fig 2) allowed us to have an overview of the temporal patterns or differentially expressed genes between dark and light melanocytes, or between the culture with KCM+ or KCM-. It showed an apparent general homogeneity, revealing no additional potential outliers and a coherent clustering of our samples according to different variables, which was valuable to discard the presence of outliers or experimental errors. The PCA showed a time-point clustering defined by the second component, revealing a major separation of the samples at 6 hours, while the samples corresponding to 12 and 24 hours clustered close to the controls (0 hours), thus suggesting an early response from melanocytes to UVB that returned again to basal levels after the first 6 hours. At 6 hours we also observed a differential response according to pigmentation defined by the first component. At 24 hours, an apparent clustering regarding the culture of light melanocytes with KCM- or KCM+ was also noticed.

Bottom Line: Our results suggest that an interaction between ribosomal proteins and the P53 signaling pathway may occur in response to UVB in both DM and LM.Furthermore, the culture with KCM+ compared with KCM- had a noticeable effect on LM.This effect includes the activation of various signaling pathways such as the mTOR pathway, involved in the regulation of cell metabolism, growth, proliferation and survival.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Physical Anthropology and Animal Physiology. University of the Basque Country UPV/EHU, Leioa, Bizkaia, Spain.

ABSTRACT
We analysed the whole-genome transcriptional profile of 6 cell lines of dark melanocytes (DM) and 6 of light melanocytes (LM) at basal conditions and after ultraviolet-B (UVB) radiation at different time points to investigate the mechanisms by which melanocytes protect human skin from the damaging effects of UVB. Further, we assessed the effect of different keratinocyte-conditioned media (KCM+ and KCM-) on melanocytes. Our results suggest that an interaction between ribosomal proteins and the P53 signaling pathway may occur in response to UVB in both DM and LM. We also observed that DM and LM show differentially expressed genes after irradiation, in particular at the first 6h after UVB. These are mainly associated with inflammatory reactions, cell survival or melanoma. Furthermore, the culture with KCM+ compared with KCM- had a noticeable effect on LM. This effect includes the activation of various signaling pathways such as the mTOR pathway, involved in the regulation of cell metabolism, growth, proliferation and survival. Finally, the comparison of the transcriptional profiles between LM and DM under basal conditions, and the application of natural selection tests in human populations allowed us to support the significant evolutionary role of MIF and ATP6V0B in the pigmentary phenotype.

No MeSH data available.


Related in: MedlinePlus