Hmga2-dependent cAMP signaling drives UVB-induced melanocyte stem cell activation

Here, we establish the oncofetal chromatin remodeling factor High mobility group AT-hook 2 (Hmga2) as a regulator of these phenotypes through a cyclic-AMP (cAMP) driven process. In this study, we identify somatic tissue expression of Hmga2 in the basal layer of hyperplastic UVB-exposed keratinocytes.

Loss of Hmga2 results in the near absence of epidermal hyperplasia, cutaneous neutrophil infiltration, and melanocyte stem cell migration to the interfollicular epidermis. RNAseq of UVB-exposed keratinocytes from wild-type and Hmga2 loss-of-function models reveals increased expression of Adenosine A1 receptor (Adora1), a negative regulator of cAMP. Administration of the cAMP pathway activator forskolin to Hmga2-/- animals is sufficient to rescue McSC migration, thus highlighting the Hmga2-cAMP axis as a regulator in the cutaneous UVB response.