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

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Date
2017
Authors
Xiang, Handan
Yuan, Lifeng
Gao, Xia
Alexander, Peter B
Lopez, Omar
Lau, Calvin
Ding, Yi
Chong, Mengyang
Sun, Tao
Chen, Rui
Liu, Si-Qi
Wu, Haiyang
Wan, Ying
Randell, Scott H
Li, Qi-Jing
Wang, Xiao-Fan
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(16 total)
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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.
Type
Journal article
Subject
UHRF1
basal stem cell
proliferation
senescence
Permalink
https://hdl.handle.net/10161/15358
Published Version (Please cite this version)
10.1038/celldisc.2017.19
Publication Info
Xiang, Handan; Yuan, Lifeng; Gao, Xia; Alexander, Peter B; Lopez, Omar; Lau, Calvin; ... Wang, Xiao-Fan (2017). UHRF1 is required for basal stem cell proliferation in response to airway injury. Cell Discov, 3. pp. 17019. 10.1038/celldisc.2017.19. Retrieved from https://hdl.handle.net/10161/15358.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Li

Qi-Jing Li

Adjunct Associate Professor in the Department of Immunology
Recent clinical success in cancer immunotherapy, including immune checkpoint blockades and chimeric antigen receptor T cells, have settled a long-debated question in the field: whether tumors can be recognized and eliminated by our own immune system, specifically, the T lymphocyte. Meanwhile, current limitations of these advanced treatments pinpoint fundamental knowledge deficits in basic T cell biology, especially in the context of tumor-carrying patients. Aiming to develop new immunotherapi
Wang

Xiao-Fan Wang

Donald and Elizabeth Cooke Distinguished Professor of Cancer Research, in the School of Medicine
The current research in the Wang laboratory mainly focuses on the elucidation of molecular nature and signaling mechanisms associated with the initiation of cellular senescence. In addition, we continue to study changes in tumor microenvironment that promotes tumor progression and metastasis, particularly how tumor cells interact with the immune system. Ultimately, we hope that our studies in these areas to lead to the development of novel therapeutics for the treatment of various types of human
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