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Gene expression profiles of skin basal layer in young, aged, and Tunicamycin treated killifish

ABSTRACT: The endoplasmic reticulum (ER) stress-response is an adaptive cellular mechanism activated by unfolded protein accumulation within the ER. Although recent evidence shows that ER stress-response is activated in aged tissues and therefore ER stress is considered as a candidate driver of aging, the spatiotemporal regulation and roles of the ER stress-response during aging remains unclear, especially in vertebrates. Using imaging, analysis we discovered that the expression of Ire1-Xbp1s in the basal layer of epidermis decline during aging, suggesting that ER stress response is involved in epidermal basal layer regulation. Furthermore, treatment with tunicamycin, a pharmacological ER stress inducer, significantly increase cell proliferation, while genetic abaltion decrease cell proliferation in epidermal basal layer. To uncover the mechanism in which Ire1-Xbp1s regulates epidermal stem cell proliferation, a novel spatial transcriptomics, the Photo-Isolation Chemistry (PIC) is conducted in young, aged, and tunicamycin treated aged epidermal basal layer of the killifish. As a result, we identified that the Ire1-Xbp1s pathway maintains young epidermal stem cell proliferation through activating a cell cycle regulator Vcp, while the age-dependent decline of glucose metabolism reduces the Ire1-Xbp1s activity, which consequently downregulates stem cells proliferation. Collectively, our study shows a previously unidentified role of ER stress-response in skin aging, which can offer insights into therapeutic targets for promoting healthy skin.

ORGANISM(S): Nothobranchius furzeri

PROVIDER: GSE287914 | GEO | 2025/12/17

REPOSITORIES: GEO

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