SOX10 targetome

We investigated cellular heterogeneity and phenotype switching in melanoma by single-cell RNA-Seq of more than 39,000 cells in patient-derived melanoma cultures. Using gene regulatory network analysis, we identified shared gene regulatory networks that underlie the extreme melanocytic and mesenchymal cell states, as well as a stable intermediate state.
This intermediate state was corroborated by a distinct open chromatin landscape and is governed among others by the transcription factors EGR3, NFATC2, and SOX6. Cells residing in this intermediate state also show an intermediate migratory phenotype, as established by single-cell migration assays.
We further studied the dynamics of the phenotypic switch from a melanocytic to a mesenchymal-like cell state by knock-down of the lineage factor SOX10. Through a dense time-series sampling and dynamic inference of gene regulatory networks, we unraveled the sequential and recurrent arrangement of transcriptional programs that play a role during this phenotype switch.
The gene regulatory networks we identified may be important in acquisition of metastatic and drug resistance potential and can therefore serve as a putative target in melanoma treatment.