Expression of The Embryonic Stem Cell Transcription Factor SOX2 in Human Skin

Abstract

SOX2 is a gene located on chromosome 3q26.33 that encodes a transcription factor important to mainte- nance of embryonic neural crest stem cell pluripotency. We have identified rare SOX2-immunoreactive cells in normal human skin at or near the established stem cell niches. Three subsets of SOX2-positive cells were de- fined in these regions: those expressing only SOX2 and those that co-expressed SOX2 and either CK20 or microphthalmia-associated transcription factor, which are consistent with dichotomous differenti- ation of SOX2-expressing precursors along neu- roendocrine (Merkel cell) or melanocytic lines, re- spectively. Examination of Merkel cell carcinomas confirmed nuclear SOX2 expression in this tumor type. In human patient melanoma, strong nuclear expression of SOX2 was noted in a subset of tu- mors, and the ability to detect SOX2 in lesional cells significantly correlated with primary tumor thick- ness in a survey cohort. To assess the potential role of SOX2 in melanoma growth, an in vivo tumori- genesis assay was used. Whereas SOX2 knockdown failed to influence proliferation of cultured mela- noma cells in vitro, tumor xenografts generated with the SOX2-knockdown cell line showed signif- icant decrease in mean tumor volume as compared with controls. In aggregate, these findings suggest that SOX2 is a novel biomarker for subpopulations of normal skin cells that reside in established stem cell niches and that might relate to Merkel cell and melanocyte ontogeny and tumorigenesis.