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

Leanne R Donahue; Chia-Hsin Hsu; Youngeun H Yang; Alex Wong; Luye An; Dahihm Kim; Andrew C White

doi:10.1016/j.jid.2026.05.007

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

J Invest Dermatol. 2026 May 26:S0022-202X(26)01218-2. doi: 10.1016/j.jid.2026.05.007. Online ahead of print.

Authors

Leanne R Donahue¹, Chia-Hsin Hsu¹, Youngeun H Yang¹, Alex Wong¹, Luye An¹, Dahihm Kim¹, Andrew C White²

Affiliations

¹ Department of Biomedical and Translational Sciences, Cornell University, Ithaca, New York, USA.
² Department of Biomedical and Translational Sciences, Cornell University, Ithaca, New York, USA. Electronic address: acw93@cornell.edu.

PMID: 42190867
DOI: 10.1016/j.jid.2026.05.007

Abstract

UVB induces an epidermal damage response, including keratinocyte hyperplasia, immune cell infiltration, and the recruitment of follicular melanocyte stem cells to the interfollicular epidermis. In this study, we establish the oncofetal chromatin remodeling factor Hmga2 (high mobility group AT-hook 2) as a regulator of these phenotypes through a 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. RNA sequencing of UVB-exposed keratinocytes from wild-type and Hmga2 loss-of-function models reveals increased expression of Adora1 (adenosine A1 receptor), a negative regulator of cAMP. Administration of the cAMP pathway activator forskolin to Hmga2^-/- animals is sufficient to rescue melanocyte stem cell migration, thus highlighting the Hmga2-cAMP axis as a regulator in the cutaneous UVB response.

Keywords: Cell migration; Mouse models; UVR.