Project 2 is dedicated to investigating the communication between melanoma cells and dermal fibroblasts to discover novel regulators of tumor heterogeneity and metastatic dissemination. We know that fibroblasts remain dormant in healthy tissues, but they become activated during wound healing to support tissue regeneration. Similarly, cancer cells can activate fibroblasts, transforming them into cancer-associated fibroblasts (CAFs). Although the mechanisms controlling this transformation are not fully understood, we believe that both cell extrinsic and cell intrinsic factors play a role in allowing melanoma cells and fibroblasts to co-evolve into various cell states, including those with metastatic potential. Through our extensive expertise in gene regulation, wound healing, skin regeneration, and single-cell/spatial transcriptomics, we aim to explore this co-evolution and define its impact on metastatic dissemination in early-stage melanomas.