GPNMB is a marker of invasive quiescent differentiated melanoma cells driven by tumor niche reprogramming

We provide evidence of the existence of a slow cycling melanoma population isolated in vivo from melanoma PDXs using the H2B-GFP system. Single cell transcriptomic analysis unveils a significant transcriptional heterogeneity of GFP-retaining slow cycling cells, defining a quiescent subpopulation of cells. These cells show a different phenotype in primary tumors and matched metastases, suggesting that tumor niche pressure drives a transcriptional reprogramming of quiescent cells during melanoma progression. Primary and metastatic melanoma MM13 and MM27 H2B-GFP PDX were sorted using fluorescence-associated cell sorters (Aria and Melody, BD Bioscience) to isolate GFP positive and GFP negative populations and analyzed using ScRNAseq.