Stage- and subunit-specific functions of polycomb repressive complex 2 in bladder urothelial formation and regeneration

摘要: ABSTRACT Urothelium is the protective lining of urinary tract. The mechanisms underlying urothelial formation and maintenance are largely unknown. Here, we report stage-specific roles PRC2 epigenetic regulators in embryonic adult progenitors. Without Eed , obligatory subunit PRC2, progenitors demonstrate reduced proliferation with concomitant dysregulation genes including Cdkn2a ( p16 ), Cdkn2b p15 ) Shh. These mutants display premature differentiation keratin 5-positive (Krt5 + basal cells ectopic expression squamous-like markers. Deletion Ezh2 major enzymatic component causes upregulation Upk3a superficial cells. Unexpectedly, / double exhibit delayed cell differentiation. Furthermore, regulates proliferative regenerative capacity prevents precocious Collectively, these findings uncover mechanism by which controls progenitor fate timing differentiation, further suggest an basis regeneration.