Single-Cell Trajectories of Melanoma Cell Resistance to Targeted Treatment

In order to identify mechanisms of melanoma treatment resistance, we applied micorofluidic scRNA-Seq to the transcripomes of a total of about 31,000 single cells obtained form A375 melanoma cell line untreated/sensitive or treated with BRAF inhibitor vemurafenib, either alone or in combination with MEK1 inihibitor cobimetinib or trametinib. Analysis by dimensionality reduction software tSNE and SOM identified a clonal heterogeneity clearly seperating all 4 possible treatment conditions. scRNA-Seq of BRAF-mutant A375 cells in 4 treatment conditions: untreated/sensitive cells, cells resistant to vemurafenib, cells double-resistant to vemurafenib and cobimetinib, cells double-resistant to vemurafenib and trametinib