Tfap2b specifies an embryonic melanocyte stem cell that retains adult multi-fate potential

Abstract

Melanocytes, our pigment producing cells, originate from neural crest-derived progenitors during embryogenesis and from multiple stem cell niches in adult tissues. Although pigmentation traits are known risk-factors for melanoma, we lack lineage markers with which to identify melanocyte stem cell populations and study their function. Here, by combining live-imaging, scRNA-seq and chemical-genetics in zebrafish, we identify the transcription factor Tfap2b as a functional marker for the melanocyte stem cell (MSC) population that resides at the dorsal root ganglia site. Tfap2b is required for only a few late-stage embryonic melanocytes, and instead is essential for MSC-dependent melanocyte regeneration. Our lineage-tracing data reveal that tfap2b-expressing MSCs have multi-fate potential, and are the cell-of-origin for a discrete number of embryonic melanocytes, large patches of adult melanocytes, and two other pigment cell types; iridophores and xanthophores. Hence, Tfap2b confers MSC identity, and thereby distinguishes MSCs from other neural crest and pigment cell lineages.