Dynamic regulation of chromatin accessibility during melanocyte stem cell activation

We sorted melanocyte nuclei from quiescent (telogen) skin, skin actively producing hair shafts (anagen), and skin exposed to UVB. With these sorted nuclei, we then utilized single-nucleus assay for transposase-accessible chromatin with high-throughput sequencing (snATAC-seq) and characterized three melanocyte lineages: quiescent McSCs (qMcSCs), activated McSCs (aMcSCs), and differentiated melanocytes (dMCs) that co-exist in all three skin conditions. Furthermore, we successfully identified differentially accessible genes and enriched transcription factor binding motifs for each melanocyte lineage. Our findings reveal potential gene regulators that determine these melanocyte cell states and provide new insights into how aMcSC chromatin states are regulated differently under divergent intrinsic and extrinsic cues. We also provide a publicly available online tool with a user-friendly interface to explore this comprehensive dataset, which will provide a resource for further studies on McSC regulation upon natural or UVB-mediated stem cell activation. Overall design: snATAC-seq library was generated from GFP+ nuclei from dorsal skin of 7-week-old Dct-rtTa; Tre-H2B-GFP mice in telogen phase or treated with Nair cream or UVB after providing drinking water containing doxycycline.