This study investigates how senescent cells influence intestinal stem cell (ISC) differentiation. The researchers identify the secreted N-terminal domain of Ptk7 as a key component of the senescence-associated secretory phenotype (SASP) that activates noncanonical Wnt/Ca²⁺ signaling through FZD7 in ISCs. This activation leads to nuclear translocation of YAP and expression of YAP/TEAD target genes, impairing ISC differentiation and crypt formation.
Secreted Ptk7 from senescent cells activates noncanonical Wnt/Ca²⁺ signaling via FZD7, leading to YAP activation and impaired ISC differentiation. Conditional deletion of Ptk7 in mice rescues these effects, highlighting its role in age-related intestinal dysfunction.
Ptk7(fl/fl) conditional Knockout mouse model developed by genOway, allowing for tissue-specific deletion of Ptk7 to study its role in ISC function and differentiation.
Aging, Intestinal stem cells, Senescence, Wnt signaling, YAP/TEAD pathway
Conditional Knockout model, LoxP-flanked Ptk7 alleles, Tissue-specific Cre recombinase, Organoid culture, ISC differentiation assays
From model design to experimental results
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