Project description:Tertiary lymphoid tissues (TLTs) are formed in systemic organs manifesting chronic inflammation. Herein, we found that the renal pelvis (RP) could form urinary tract-associated lymphoid tissues (UTALTs) in a TLT-formation manner in humans and mice with chronic kidney disease (CKD), regardless of infectious pyelonephritis. Furthermore, collagen type XVII alpha 1 chain (COL17A1), localized ectopically to the transitional epithelium (TE) covering the UTALT, where it participated in TE development via immunological stimulation of UTALT-forming cells.
Project description:Head and Neck Squamous Cell Carcinoma (HNSC) originates from specialized epithelium, and identifying lineage-specific oncogenes is crucial for understanding tumor progression. In this study, we identified COL17A1 as a potential core regulator in HNSC. To characterize the transcriptional landscape and molecular mechanisms regulated by COL17A1, we performed bulk RNA-sequencing on the human oral squamous cell carcinoma cell line, SAS. We compared the gene expression profiles of control cells (transfected with negative control siRNA) against COL17A1-depleted cells (transfected with COL17A1-specific siRNAs). This dataset reveals that depletion of COL17A1 leads to the dismantlement of a specific "Partial-EMT" gene module and induces a metabolic shift, highlighting its role in maintaining the malignant phenotype of HNSC cells.
Project description:Collagen 17A1 (COL17A1) is induced in urothelium under disease conditions of urinary system organs, such as chronic nephritis and urinary obstruction. Thus, the ureters of Col17a1-knock out (KO) mice were injured by unilateral ureteral obsruction (UUO), and the gene expression was compared with those of wild-tyoe (WT).
Project description:Hair loss is one of the typical aging phenotypes in mammals, yet the underlying mechanism(s) is unclear. Here we report that hair follicle stem cell (HFSC) aging causes the stepwise miniaturization of hair follicles and eventual hair loss both in wild-type mice and in humans. In vivo fate analysis of HFSCs revealed that the DNA damage response in HFSCs causes proteolysis of Type XVII Collagen (COL17A1/BP180) to trigger “HFSC aging”, characterized by their loss of stemness signature and epidermal commitment. Those aged HFSCs are cyclically eliminated from the skin through their terminal epidermal differentiation, thereby causing hair follicle miniaturization. That process can be recapitulated by Col17a1 deficiency and prevented by forced maintenance of COL17A1 in HFSCs, demonstrating that stem cell homeostasis is the keystone against ultimate execution of the tissue/organ aging program.