Browsing by Subject "Melanocytes"

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    Cell-type-specific eQTL of primary melanocytes facilitates identification of melanoma susceptibility genes
    (Cold Spring Harbor Laboratory Press, 2018-11) Zhang, Tongwu; Choi, Jiyeon; Kovacs, Michael A.; Shi, Jianxin; Xu, Mai; Goldstein, Alisa M.; Trower, Adam J.; Bishop, D. Timothy; Iles, Mark M.; Duffy, David L.; MacGregor, Stuart; Amundadottir, Laufey T.; Law, Matthew H.; Loftus, Stacie K.; Pavan, William J.; Brown, Kevin M.; Epidemiology, School of Public Health
    Most expression quantitative trait locus (eQTL) studies to date have been performed in heterogeneous tissues as opposed to specific cell types. To better understand the cell-type-specific regulatory landscape of human melanocytes, which give rise to melanoma but account for <5% of typical human skin biopsies, we performed an eQTL analysis in primary melanocyte cultures from 106 newborn males. We identified 597,335 cis-eQTL SNPs prior to linkage disequilibrium (LD) pruning and 4997 eGenes (FDR < 0.05). Melanocyte eQTLs differed considerably from those identified in the 44 GTEx tissue types, including skin. Over a third of melanocyte eGenes, including key genes in melanin synthesis pathways, were unique to melanocytes compared to those of GTEx skin tissues or TCGA melanomas. The melanocyte data set also identified trans-eQTLs, including those connecting a pigmentation-associated functional SNP with four genes, likely through cis-regulation of IRF4 Melanocyte eQTLs are enriched in cis-regulatory signatures found in melanocytes as well as in melanoma-associated variants identified through genome-wide association studies. Melanocyte eQTLs also colocalized with melanoma GWAS variants in five known loci. Finally, a transcriptome-wide association study using melanocyte eQTLs uncovered four novel susceptibility loci, where imputed expression levels of five genes (ZFP90, HEBP1, MSC, CBWD1, and RP11-383H13.1) were associated with melanoma at genome-wide significant P-values. Our data highlight the utility of lineage-specific eQTL resources for annotating GWAS findings, and present a robust database for genomic research of melanoma risk and melanocyte biology.
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    Topology of feather melanocyte progenitor niche allows complex pigment patterns to emerge
    (American Association for the Advancement of Science, 2013) Lin, S. J.; Foley, J.; Jiang, T. X.; Yeh, C. Y.; Wu, P.; Foley, A.; Yen, C. M.; Huang, Y. C.; Chen, C. F.; Reeder, B.; Jee, S. H.; Widelitz, R. B.; Chuong, C. M.; Dermatology, School of Medicine
    Color patterns of bird plumage affect animal behavior and speciation. Diverse patterns are present in different species and within the individual. Here, we study the cellular and molecular basis of feather pigment pattern formation. Melanocyte progenitors are distributed as a horizontal ring in the proximal follicle, sending melanocytes vertically up into the epithelial cylinder, which gradually emerges as feathers grow. Different pigment patterns form by modulating the presence, arrangement, or differentiation of melanocytes. A layer of peripheral pulp further regulates pigmentation via patterned agouti expression. Lifetime feather cyclic regeneration resets pigment patterns for physiological needs. Thus, the evolution of stem cell niche topology allows complex pigment patterning through combinatorial co-option of simple regulatory mechanisms.