In vitro modeling of hyperpigmentation associated to neurofibromatosis type 1 using melanocytes derived from human embryonic stem cells

Significance

There are few suitable laboratory models for human pigmentation disease. Neurofibromatosis type 1 (NF1) is a common neurocutaneous disease whose initial symptoms in all patients are “café-au-lait” macules and overall skin hyperpigmentation. To analyze the molecular mechanisms associated with this phenotype, we have developed an in vitro model of NF1 based on human embryonic stem cells (hESCs). Melanocytes derived from NF1 hESCs reproduced the hyperpigmentation phenotype in vitro and were characterized by deregulation of melanogenesis factors. The model allowed us to identify the cellular pathways involved in this phenotype. The hyperpigmentation phenotype could be rescued by small molecules, demonstrating the potential of pluripotent stem cells as models for pigmentation disorders.