Fialkowski Allison C, Levy Denise J, Watkins-Chow Dawn E, Palmer Joseph W, Darji Roshan, Tiwari Hemant K, Pavan William J, Harris Melissa L
Department of Biostatistics.
University of Alabama at Birmingham, Birmingham, AL, and.
G3 (Bethesda). 2019 Mar 7;9(3):817-827. doi: 10.1534/g3.118.200965.
Age-related hair graying is caused by malfunction in the regenerative potential of the adult pigmentation system. The retention of hair color over the life of an organism is dependent on the ability of the melanocyte stem cells and their progeny to produce pigment each time a new hair grows. Age-related hair graying is variable in association with genetic background suggesting that quantitative trait loci influencing this trait can be identified. Identification of these quantitative trait loci may lead to the discovery of novel and interesting genes involved in stem cell biology and/or melanogenesis. With this in mind we developed previously a sensitized, mouse modifier screen and discovered that the DBA/1J background is particularly resistant to melanocyte stem cell differentiation in comparison to the C57BL/6J background. Melanocyte stem cell differentiation generally precedes hair graying and is observed in melanocyte stem cells with age. Using quantitative trait loci analysis, we have now identified three quantitative trait loci on mouse chromosomes 7, 13, and X that are associated with DBA/1J-mediated variability in melanocyte stem cell differentiation. Taking advantage of publicly-available mouse sequence and variant data, in silico protein prediction programs, and whole genome gene expression results we describe a short list of potential candidate genes that we anticipate to be involved in melanocyte stem cell biology in mice.
与年龄相关的头发变白是由成年色素沉着系统再生潜能的功能失调引起的。生物体一生中头发颜色的保持取决于黑素细胞干细胞及其后代在每次新头发长出时产生色素的能力。与年龄相关的头发变白因遗传背景而异，这表明可以识别影响该性状的数量性状基因座。识别这些数量性状基因座可能会导致发现涉及干细胞生物学和/或黑素生成的新颖有趣的基因。考虑到这一点，我们之前开发了一种敏感的小鼠修饰基因筛选方法，并发现与C57BL/6J背景相比，DBA/1J背景对黑素细胞干细胞分化具有特别的抗性。黑素细胞干细胞分化通常先于头发变白，并且随着年龄的增长在黑素细胞干细胞中可以观察到。使用数量性状基因座分析，我们现在已经在小鼠7号、13号和X染色体上鉴定出三个数量性状基因座，它们与DBA/1J介导的黑素细胞干细胞分化变异性相关。利用公开可用的小鼠序列和变异数据、计算机蛋白质预测程序以及全基因组基因表达结果，我们描述了一份潜在候选基因的简短清单，我们预计这些基因参与小鼠黑素细胞干细胞生物学过程。
