UHRF1 is required for basal stem cell proliferation in response to airway injury

• DOI: 10.1038/celldisc.2017.19
• Publication Date: 2017-06-13T10:11:03Z
• Authors: Handan Xiang; Lifeng Yuan; Xia Gao; Peter B Alexander; Omar Lopez; Calvin Lau; Yi Ding; Mengyang Chong; Tao Sun; Rui Chen; Si-Qi Liu; Haiyang Wu; Ying Wan; Scott H Randell; Qi-Jing Li; Xiao-Fan Wang
• Keywords: Senescence

Cellular senescence is a cell fate characterized by an irreversible cycle arrest, but the molecular mechanism underlying this hallmark remains poorly understood. Through unbiased search for novel regulators in airway basal cells, we discovered that epigenetic regulator ubiquitin-like with PHD and ring finger domain-containing protein 1 (UHRF1) critical regulating progression. Upon injury, cells mouse rapidly induce expression of UHRF1 order to stimulate stem proliferation tissue repair. Targeted depletion Uhrf1 specifically causes profound defect Consistently, cultured primary human lacking do not exhibit death or differentiation phenotypes undergo spontaneous program senescence. Mechanistically, loss induces G1 arrest abrogating DNA replication factory formation as evidenced proliferating nuclear antigen (PCNA) puncta inability enter first cycle. This partially mediated p15 pathway. Overall, our study provides evidence indispensable role somatic during process regeneration.