UVB damage response of dermal stem cells as melanocyte precursors compared to keratinocytes, melanocytes, and fibroblasts from human foreskin

• Published in: Journal of photochemistry and photobiology. B, Biology Vol. 220; p. 112216
• Main Authors: Mhamdi-Ghodbani, Mouna, Starzonek, Christin, Degenhardt, Sarah, Bender, Marc, Said, Mohammed, Greinert, Rüdiger, Volkmer, Beate
• Format: Journal Article
• Language: English
• Published: Lausanne Elsevier B.V 01.07.2021; Elsevier BV
• Subjects: Apoptosis; Carcinogenesis; Carcinogens; Cell cycle; Cell differentiation; Comparative studies; Cyclobutane; Cyclobutane pyrimidine dimers; Deoxyribonucleic acid; Dermal stem cell; Dimers; DNA; DNA damage; DNA repair; Fibroblasts; Irradiation; Keratinocytes; Melanocytes; Melanoma; Neural crest; Neural stem cells; Precursors; Radiation damage; Repair; S phase; Skin; Stem cells; Ultraviolet radiation; Ultraviolet radiation; Dermal stem cell; DNA repair; Cell cycle; Apoptosis
• ISSN: 1011-1344; 1873-2682
• DOI: 10.1016/j.jphotobiol.2021.112216

Ultraviolet B (UVB) radiation induces mutagenic DNA photolesions in skin cells especially in form of cyclobutane pyrimidine dimers (CPDs). Protection mechanisms as DNA repair and apoptosis are of great importance in order to prevent skin carcinogenesis. In human skin, neural crest-derived precursors of melanocytes, the dermal stem cells (DSCs), are discussed to be at the origin of melanoma. Although they are constantly exposed to solar UV radiation, it is still not investigated how DSCs cope with UV-induced DNA damage. Here, we report a comparative study of the DNA damage response after irradiation with a physiological relevant UVB dose in DSCs in comparison to fibroblasts, melanocytes and keratinocytes isolated from human foreskin. Within our experimental settings, DSCs were able to repair DNA photolesions as efficient as the other skin cell types with solely keratinocytes repairing significantly faster. Interestingly, only fibroblasts showed significant alterations in cell cycle distribution in terms of a transient S phase arrest following irradiation. Moreover, with the applied UVB dose none of the examined cell types was prone to UVB-induced apoptosis. This may cause persistent genomic alterations and in case of DSCs it may have severe consequences for their daughter cells, the differentiated melanocytes. Altogether, this is the first study demonstrating a similar UV response in dermal stem cells compared to differentiated skin cells. [Display omitted] •Dermal stem cells (DSCs), fibroblasts, keratinocytes and melanocytes isolated from human foreskin.•DNA damage response of DSCs after UVB irradiation was similar to differentiated skin cells.•Cell cycle progression of the skin cells differed after UVB irradiation.•Low-dose UVB irradiation did not induce apoptosis.