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

dc.contributor.author Xiang, H
dc.contributor.author Yuan, Lifeng
dc.contributor.author Gao, Xia
dc.contributor.author Alexander, Peter
dc.contributor.author Lopez, Omar
dc.contributor.author Lau, C
dc.contributor.author Ding, Y
dc.contributor.author Chong, Mengyang
dc.contributor.author Sun, T
dc.contributor.author Chen, R
dc.contributor.author Liu, S-Q
dc.contributor.author Wu, H
dc.contributor.author Wan, Y
dc.contributor.author Randell, Scott Howard
dc.contributor.author Li, Qi-Jing
dc.contributor.author Wang, Xiao-Fan
dc.coverage.spatial England
dc.date.accessioned 2017-08-25T19:58:52Z
dc.date.available 2017-08-25T19:58:52Z
dc.date.issued 2017
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/28626588
dc.identifier.issn 2056-5968
dc.identifier.uri http://hdl.handle.net/10161/15358
dc.description.abstract Cellular senescence is a cell fate characterized by an irreversible cell cycle arrest, but the molecular mechanism underlying this senescence hallmark remains poorly understood. Through an unbiased search for novel senescence regulators in airway basal cells, we discovered that the epigenetic regulator ubiquitin-like with PHD and ring finger domain-containing protein 1 (UHRF1) is critical for regulating cell cycle progression. Upon injury, basal cells in the mouse airway rapidly induce the expression of UHRF1 in order to stimulate stem cell proliferation and tissue repair. Targeted depletion of Uhrf1 specifically in airway basal cells causes a profound defect in cell cycle progression. Consistently, cultured primary human basal cells lacking UHRF1 do not exhibit cell death or differentiation phenotypes but undergo a spontaneous program of senescence. Mechanistically, UHRF1 loss induces G1 cell cycle arrest by abrogating DNA replication factory formation as evidenced by loss of proliferating cell nuclear antigen (PCNA) puncta and an inability to enter the first cell cycle. This proliferation defect is partially mediated by the p15 pathway. Overall, our study provides the first evidence of an indispensable role of UHRF1 in somatic stem cells proliferation during the process of airway regeneration.
dc.language eng
dc.relation.ispartof Cell Discov
dc.relation.isversionof 10.1038/celldisc.2017.19
dc.subject UHRF1
dc.subject basal stem cell
dc.subject proliferation
dc.subject senescence
dc.title UHRF1 is required for basal stem cell proliferation in response to airway injury.
dc.type Journal article
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/28626588
pubs.begin-page 17019
pubs.organisational-group Basic Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Immunology
pubs.organisational-group Institutes and Centers
pubs.organisational-group Pharmacology & Cancer Biology
pubs.organisational-group School of Medicine
pubs.publication-status Published online
pubs.volume 3


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