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Arash Chitsazan, Pamela Mukhopadhyay, Blake Ferguson, Herlina Y

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1 Keratinocyte Cytokine Networks Associated with Human Melanocytic Nevus Development 
Arash Chitsazan, Pamela Mukhopadhyay, Blake Ferguson, Herlina Y. Handoko, Graeme J. Walker  Journal of Investigative Dermatology  Volume 139, Issue 1, Pages (January 2019) DOI: /j.jid Copyright © 2018 The Authors Terms and Conditions

2 Figure 1 Gene networks in the skin. (a) Gene network analysis showing the top 1,000 genes (all P < 0.05) up-regulated in anagen versus telogen (P < 0.05) of mouse dorsal skin. (b) Gene network for genes down-regulated in anagen. (c) Pathway annotations of genes up-regulated in mouse BCC and anagen show overlapping cellular signaling pathways that are unique to BCC or anagen or are overlapping between the two processes. (d) Schematic diagram representing the multiple ways in which keratinocyte changes can result in increased production of keratinocyte cytokines that are melanocyte mitogens. These can include changes in (i) keratins,(ii) ribosomal subunit genes, (iii) Shh signaling genes, and (iv) secretory cytokines. (e–g) Pathway annotations of the top 1,000 genes positively correlated with MITF expression (r > 0.6, P < 0.05) in (e) human normal abdomen and (f) leg skin and (g) human BCC. BCC, basal cell carcinoma. Journal of Investigative Dermatology  , DOI: ( /j.jid ) Copyright © 2018 The Authors Terms and Conditions

3 Figure 2 Gene expression correlations in the skin. (a) Overview of strategy for testing whether genes and pathways that, when mutated, induce nevus-like lesions in the mouse may also be associated with melanocyte activation in human skin. Candidate mechanisms are tested in terms of gene expression correlations across the GTEx normal human skin cohorts and a human BCC cohort. Arrows indicate gene expression correlations associated with putative up-regulation of melanocytes (via MITF up-regulation). (b) Heat map based on correlation (r) values between cytokine, melanocyte, and mast cell genes. Red indicates high correlation, and yellow indicates low correlation. Based on pooled analysis of all GTEx skin from both the abdomen and leg cohorts. (c) Heat map based on correlation (r) values. Red indicates high correlation, and yellow indicates low. Based on r values from gene expression in the cohort of BCCs (analyzed from Jee et al., 2015). BCC, basal cell carcinoma. Journal of Investigative Dermatology  , DOI: ( /j.jid ) Copyright © 2018 The Authors Terms and Conditions


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