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Persistent JunB Activation in Fibroblasts Disrupts Stem Cell Niche Interactions Enforcing Skin Aging [RNA-seq]

ABSTRACT: Fibroblasts residing in the connective tissue of all organs constitute the stem cell niche particularly in connective tissue rich organs like skin. Though the impact of the connective tissue resident fibroblasts on stem cell niches and organ aging is an emerging concept, the underlying mechanisms are largely unresolved. Here, we report a novel mechanism of redox-dependent activation of the transcription factor JunB, which through concomitant upregulation of cyclin dependent kinase inhibitor p16INK4A and repression of IGF-1 dependent cell growth and protein translation initiates the installment of irreversible fibroblast senescence. Fibroblast senescence in turn profoundly disrupts the metabolic and structural niche and its essential interactions with different stem cells thus enforcing depletion of stem cells pools and skin tissue decline. In fact, silencing of JunB in a fibroblast niche-specific knock out mouse - by the reinstatement of IGF-1 and p16 levels - fully restored skin stem cell pools and overall tissue integrity of the skin. We here uncovered a previously unreported role of JunB in the control of the endogenous connective tissue niche and identified promising targets to combat skin aging and associated pathologies.

ORGANISM(S): Mus musculus

PROVIDER: GSE180008 | GEO | 2021/07/16

REPOSITORIES: GEO

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