Revealing the UV response of melanocytes in xeroderma pigmentosum group A using patient-derived induced pluripotent stem cells.
J Dermatol Sci
; 2024 Jun 22.
Article
en En
| MEDLINE
| ID: mdl-39033075
ABSTRACT
BACKGROUND:
Xeroderma pigmentosum (XP) is characterized by photosensitivity that causes pigmentary disorder and predisposition to skin cancers on sunlight-exposed areas due to DNA repair deficiency. Patients with XP group A (XP-A) develop freckle-like pigmented maculae and depigmented maculae within a year unless strict sun-protection is enforced. Although it is crucial to study pigment cells (melanocytes MCs) as disease target cells, establishing MCs in primary cultures is challenging.OBJECTIVE:
Elucidation of the disease pathogenesis by comparison between MCs differentiated from XP-A induced pluripotent stem cells (iPSCs) and healthy control iPSCs on the response to UV irradiation.METHODS:
iPSCs were established from a XP-A fibroblasts and differentiated into MCs. Differences in gene expression profiles between XP-A-iPSC-derived melanocytes (XP-A-iMCs) and Healthy control iPSC-derived MCs (HC-iMCs) were analyzed 4 and 12â¯h after irradiation with 30 or 150â¯J/m2 of UV-B using microarray analysis.RESULTS:
XP-A-iMCs expressed SOX10, MITF, and TYR, and showed melanin synthesis. Further, XP-A-iMCs showed reduced DNA repair ability. Gene expression profile between XP-A-iMCs and HC-iMCs revealed that, numerous gene probes that were specifically upregulated or downregulated in XP-A-iMCs after 150-J/m2 of UV-B irradiation did not return to basal levels. Of note that apoptotic pathways were highly upregulated at 150â¯J/m2 UV exposure in XP-A-iMCs, and cytokine-related pathways were upregulated even at 30â¯J/m2 UV exposure.CONCLUSION:
We revealed for the first time that cytokine-related pathways were upregulated even at low-dose UV exposure in XP-A-iMCs. Disease-specific iPSCs are useful to elucidate the disease pathogenesis and develop treatment strategies of XP.
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Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
J Dermatol Sci
Asunto de la revista:
DERMATOLOGIA
Año:
2024
Tipo del documento:
Article