Genome-wide chromatin accessibility analysis of MRTF-active subpopulations in human basal cell carcinoma

Tumor heterogeneity and lack of knowledge about resistant cell states remain a significant barrier to effective targeted cancer therapies. Basal cell carcinomas (BCCs) uniformly depend on Hedgehog (Hh)/Gli signaling for cell growth. We previously identified a nuclear myocardin-related transcription factor (nMRTF) resistance pathway that amplifies Gli1 activity, but nMRTF cell state and key factors driving its accumulation remain unknown. Here, we use three surface markers (LYPD3, TACSTD2, and LY6D) to isolate the nMRTF subpopulation and analyze chromatin accessibility profiles. naive human BCC tumors were processed into single-cell suspension and FACS sorted based on ItgA6, LYPD3, TACSTD2, and LY6D expression levels. Two tumors from different patients were sorted into surface marker positive and surface marker negative groups, with two biological replicates per group. One BCC tumor from a patient with Gorlin syndrome was split into two biological replicates and sorted based on ItgA6 expression only.