Expression analysis of melanocyte stem cells from Mitfmi-vga9/+ mice reveals a role for MITF in the transcriptional regulation of innate immune gene expression. Mus musculus

Melanocyte stem cells (McSCs) and mouse models of hair graying serve as useful systems to uncover mechanisms involved in stem cell self-renewal and the maintenance of regenerating tissues. Interested in assessing genetic variants of hair graying, we found that the Mitfmi-vga9/+ strain of mice is susceptible to loss of McSC maintenance via ectopic McSC differentiation. Based on transcriptome and molecular analyses of Mitfmi-vga9/+ mice we report a novel role for MITF in the regulation of systemic innate immune gene expression. We also demonstrate that viral mimic (poly I:C) is sufficient to expose genetic susceptibility to hair graying. These observations point to a critical suppressor of innate immunity and the consequences of its dysregulation, and for melanocytes, both may have particular implications for the autoimmune, depigmenting disease vitiligo. Overall design: RNA-seq gene expression analysis was performed on melanocyte stem cells isolated from wildtype and Mitfmi-vga9/+ animals. These melanocyte stem cells were isolated from 8-week-old mice using flow cytometry. Melanocyte stem cells from approximately 10, 8-week-old animals were pooled to generate enough RNA to serve as one biological replicate. RNA-seq analysis was performed in biologial triplicate for each genotype.