Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Microarray analysis of B16 cells in pigmentation oscillator

ABSTRACT: Cellular homeostasis is an outcome of complex interacting processes with nonlinear feedbacks that span spatiotemporal scales. Skin tanning is one such dynamic response that maintains genome integrity of epidermal cells. While pathways underlying hyperpigmentation cascade are recognized, negative feedback regulatory loops that can dampen the activated melanogenesis process are not completely understood. By designing a pigmentation oscillator, in this study we delineate the role of interferon gamma (IFN-γ) signaling in skin pigmentation homeostasis. IFN-γ signaling reversibly controls maturation of the key organelle melanosome by concerted regulation of several pigmentation genes. We show that this temporal effect is mediated through interferon regulatory factor-1 (IRF-1) independent of the central regulator microphthalmia-associated transcription factor (MITF). Chronic expression of IFN-γ in mouse and human skin shows hypopigmentation phenotype, further providing a strong support to the under-appreciated function of IFN-γ in skin pigmentation. Our studies thus reveal the hitherto missing link between immune system and pigmentation, which may have implications in depigmentary and malignant cutaneous disorders. there are 12 samples from two consecutive cycles of pigmentation oscillator, termed set 1 and set 2 analysis is performed wrt to day 0 of first cycle

ORGANISM(S): Mus musculus

SUBMITTER: vivek Natarajan

PROVIDER: E-GEOD-54359 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

IFN-γ signaling maintains skin pigmentation homeostasis through regulation of melanosome maturation.

Natarajan Vivek T VT Ganju Parul P Singh Archana A Vijayan Vinaya V Kirty Kritika K Yadav Shalini S Puntambekar Shraddha S Bajaj Sonali S Dani Prachi P PP Kar Hemanta K HK Gadgil Chetan J CJ Natarajan Krishnamurthy K Rani Rajni R Gokhale Rajesh S RS

Proceedings of the National Academy of Sciences of the United States of America 20140128 6

Cellular homeostasis is an outcome of complex interacting processes with nonlinear feedbacks that can span distinct spatial and temporal dimensions. Skin tanning is one such dynamic response that maintains genome integrity of epidermal cells. Although pathways underlying hyperpigmentation cascade are recognized, negative feedback regulatory loops that can dampen the activated melanogenesis process are not completely understood. In this study, we delineate a regulatory role of IFN-γ in skin pigme ...[more]

PMID: 24474804

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Project description:Interferon-gamma (IFN-gamma) is approved as a drug to treat chronic granulomatous disease and osteopetrosis and is also used in hyperimmunoglobulin E syndromes. These primary immunodeficiencies involve defects in neutrophils/polymorphonuclear cells. Neutrophils mature in the bone marrow and then enter the blood where they quickly undergo apoptotic cell death with a half-life of 5-10 hours. Therefore we reasoned that IFN-gamma might exert its effects on neutrophils via prolonged exposure to cells undergoing maturation toward a terminally differentiated state in the marrow rather than by its brief exposure to short-lived circulating cells. To explore this possibility we made use of PLB-985 cells which are a myeloblast-like myeloid cell line that can be differentiated into a mature, neutrophil-like state by treatment with various agents including DMSO. In initial studies we investigated transcription and protein expression in PLB-985 cells undergoing DMSO-mediated maturation in the presence or absence of IFN-gamma and identified several classes of immunity related genes that were differentially expressed in the presence of the drug and could potentially explain the immune supportive properties of IFN-gamma. Next we explored if the effect of IFN-gamma on expression of these genes is dependent on whether the cells are undergoing maturation; to do this we compared the effects of IFN-gamma on cells cultured with and without DMSO. For a subset of genes the expression level changes caused by IFN-gamma were much greater in maturing cells than non-maturing cells. These findings indicate that developmental changes associated with cell maturation can modulate the effects of IFN-gamma and supports our hypothesis that the effects of the drug on developing neutrophils in the bone marrow may be very different from its effects on mature cells in the blood. We also compared the effects on gene expression of applying IFN-gamma either during DMSO mediated PLB-985 cell maturation or after maturation i.e. IFN-gamma was applied to already mature cells. For some genes we found that IFN-gamma applied to mature cells caused large changes in expression similar to those seen when IFN-gamma was applied during maturation, however for other genes no effect was seen when drug was applied to mature cells but large effects were seen when drug was applied during DMSO treatment. This data suggests that, in the former class of genes, the effects of IFN-gamma application during maturation are largely the result of the effects of the drug on cells approaching full maturity but in the latter class of genes the effects of IFN-gamma only become apparent when it is present throughout maturation. This further supports our hypothesis that the effects of IFN-gamma are modulated by developmental changes associated with cell maturation.

Dataset Information

Microarray analysis of B16 cells in pigmentation oscillator

Publications

IFN-γ signaling maintains skin pigmentation homeostasis through regulation of melanosome maturation.

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