Insights into Human Melanocyte Development and Characteristics through Pluripotent Stem Cells Combined with Single-Cell Sequencing

Many human pigment-related diseases are closely linked to melanocytes. However, our understanding of human melanocyte development has primarily relied on studies conducted on animal models which cannot fully simulate the biological characteristics and disease manifestations of humans. The utilization of pluripotent stem cells (PSCs) has shown immense potential in exploring human developmental biology. In this study, combination of human PSCs differentiation model and single-cell sequencing analysis was conducted to uncover the cellular heterogeneity and dynamic changes in biological characteristics, differentiation trajectory, and signaling interactions during melanocyte development. By integrating single-cell data from normal human melanocytes, we confirmed that induced melanocytes derived from PSCs encompassed all stages of human melanocyte development. Compared to mouse melanocytes, induced melanocytes better mimic the characteristics of human melanocytes, particularly at early stage of development. Exploration of cell-cell communication revealed the interactions among sub-populaiton of induced melanocytes involved pathways including BMP, WNT, TGF-beta, etc. Additionally, surface markers of melanocyte stem cells were screened and PDGFRB was identified as a potential marker. Collectively, these findings demonstrate that the PSCs can effectively stimulate human melanocyte development, providing a valuable tool for further investigation of melanocyte-related diseases. Overall design: In this study, induced pluripotent stem cells (iPSCs) and WA09 (H9) human embryonic stem cells were used. Melanocytes differentiated from iPSCs were collected at Day 23, Day 32, and Day 44, and then subjected to scRNA-seq analysis.