Wip1 deficiency impairs haematopoietic stem cell function via p53 and mTORC1 pathways

Zhiyang Chen, Weiwei Yi, Yohei Morita, Hu Wang, Yusheng Cong, Jun-Ping Liu, Zhicheng Xiao, K. Lenhard Rudolph, Tao Cheng and Zhenyu Ju ()
Additional contact information
Zhiyang Chen: Institute of Aging Research, Leibniz Link Partner Group on Stem Cell Aging, Hangzhou Normal University School of Medicine
Weiwei Yi: Institute of Aging Research, Leibniz Link Partner Group on Stem Cell Aging, Hangzhou Normal University School of Medicine
Yohei Morita: Leibniz Institute for Age Research—Fritz Lipmann Institute
Hu Wang: Institute of Aging Research, Leibniz Link Partner Group on Stem Cell Aging, Hangzhou Normal University School of Medicine
Yusheng Cong: Institute of Aging Research, Leibniz Link Partner Group on Stem Cell Aging, Hangzhou Normal University School of Medicine
Jun-Ping Liu: Institute of Aging Research, Leibniz Link Partner Group on Stem Cell Aging, Hangzhou Normal University School of Medicine
Zhicheng Xiao: Monash University
K. Lenhard Rudolph: Leibniz Institute for Age Research—Fritz Lipmann Institute
Tao Cheng: State Key Laboratory of Experimental Hematology, Institute of Hematology, Chinese Academy of Medical Sciences and Peking Union Medical College
Zhenyu Ju: Institute of Aging Research, Leibniz Link Partner Group on Stem Cell Aging, Hangzhou Normal University School of Medicine

Nature Communications, 2015, vol. 6, issue 1, 1-11

Abstract: Abstract Wild-type p53-induced phosphatase 1 (Wip1) negatively regulates several tumour suppressor and DNA damage response pathways. However, the impact of Wip1 on haematopoietic stem cell (HSC) homeostasis and aging remains unknown. Here we show that Wip1 is highly expressed in HSCs but decreases with age. Wip1-deficient (Wip1−/−) mice exhibited multifaceted HSC aging phenotypes, including the increased pool size and impaired repopulating activity. Deletion of p53 rescued the multilineage repopulation defect of Wip1−/− HSCs without affecting cellular senescence or apoptosis, indicating that the Wip1–p53 axis regulates HSC differentiation in a manner independent of conventional p53 pathways. However, p53 deletion did not influence the increased HSC pool size in Wip1−/− mice. Interestingly, the expansion of HSCs in Wip1−/− mice was due to an mTORC1-mediated HSC proliferation. Thus, our study reveals a mechanism of stem cell aging, in which distinct effects of p53 and mTORC1 pathways on HSC aging are governed by Wip1.

Date: 2015
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms7808 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7808

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms7808

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().