PDX melanoma of non-genetic resistance Mel006 was investigated at deep resolution on transcriptional and chromatin levels. 10X scRNA-seq and 10X scATAC-seq data were generated in this model at 5 different timepoints during treatment with DT. On transcriptional part, several subpopulations known to be present at MRD with different technologies were found back, validating the quality of our data : NCSC, invasive cells, SMC cells, hyper pigmented cells. Moreover, a highly distinct new subpopulation, not characterized yet in this model, emerged. This subpopulation has specific markers related to stress through AP-1 signaling and shows a strong gene regulatory network regulated by AP-1 factors using SCENIC tool. This subpopulation will be of high interest for further investigations as AP-1 already been shown to be involved in invasion and early resistance to treatment. Looking at dynamic of subpopulations with time under treatment, NCSC state was found to be a transient state mainly present at MRD, while cells enriched for pigmentation signatures were found to be enriched on early time after relapse, raising the question of their involvement in resistance. scATAC-seq data shown good quality. However, integrating those scATAC-seq data with scRNA-seq,specific enhancers of subpopulations of interest were failed to be identified for subsequent lineage tracing investigations. To circumvent this issue, the new 10X Multi-Ome technology that allows to get transcriptional and chromatin accessibility measures simultaneously in same cells was performed on same model. Those data were pre-analyzed and shows overall good quality and will need further investigation.
