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

Nature Communications

Volumn 6, Issue , 2015, Pages

  Chen, Zhiyang ^a,b   Yi, Weiwei ^a   Morita, Yohei ^b   Wang, Hu ^a   Cong, Yusheng ^a   Liu, Jun Ping ^a   Xiao, Zhicheng ^c   Rudolph, K Lenhard ^b   Cheng, Tao ^d   Ju, Zhenyu ^a  

^a HANGZHOU NORMAL UNIVERSITY   (China)

^b FRITZ LIPMANN INSTITUTE   (Germany)

^c MONASH UNIVERSITY   (Australia)

^d INSTITUTE OF HEMATOLOGY AND BLOOD DISEASES HOSPITAL   (China)

Author keywords

[No Author keywords available]

Indexed keywords

MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; PROTEIN; PROTEIN P53; UNCLASSIFIED DRUG; WIP1 PROTEIN; ANTINEOPLASTIC ANTIMETABOLITE; CCT007093; CYCLOPENTANE DERIVATIVE; FLUOROURACIL; MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1; MULTIPROTEIN COMPLEX; PHOSPHOPROTEIN PHOSPHATASE; PROTEIN PHOSPHATASE 2C; TARGET OF RAPAMYCIN KINASE; THIOPHENE DERIVATIVE;

AGE STRUCTURE; APOPTOSIS; CELLS AND CELL COMPONENTS; ENZYME ACTIVITY; GENE EXPRESSION; HOMEOSTASIS; PHENOTYPE; SENESCENCE;

AGING; ANIMAL CELL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; CELL AGING; CELL DIFFERENTIATION; CELL FUNCTION; CONTROLLED STUDY; HEMATOPOIETIC STEM CELL; MOUSE; NONHUMAN; PHENOTYPE; PROTEIN DEFICIENCY; PROTEIN EXPRESSION; SENESCENCE; ANIMAL; ANTAGONISTS AND INHIBITORS; BONE MARROW CELL; BONE MARROW TRANSPLANTATION; CELL CYCLE; CFU COUNTING; CYTOLOGY; DRUG EFFECTS; FLOW CYTOMETRY; GENETICS; HOMEOSTASIS; KNOCKOUT MOUSE; METABOLISM; REAL TIME POLYMERASE CHAIN REACTION; WESTERN BLOTTING;

MUS;

ANIMALS; ANTIMETABOLITES, ANTINEOPLASTIC; APOPTOSIS; BLOTTING, WESTERN; BONE MARROW CELLS; BONE MARROW TRANSPLANTATION; CELL AGING; CELL CYCLE; COLONY-FORMING UNITS ASSAY; CYCLOPENTANES; FLOW CYTOMETRY; FLUOROURACIL; HEMATOPOIETIC STEM CELLS; HOMEOSTASIS; MICE; MICE, KNOCKOUT; MULTIPROTEIN COMPLEXES; PHOSPHOPROTEIN PHOSPHATASES; REAL-TIME POLYMERASE CHAIN REACTION; THIOPHENES; TOR SERINE-THREONINE KINASES; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84928038734     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms7808     Document Type: Article

References (50)

1. Orkin, S. H. & Zon, L. I. Hematopoiesis: An evolving paradigm for stem cell biology. Cell 132, 631-644 (2008).
2. Florian, M. C. et al. A canonical to non-canonical Wnt signalling switch in haematopoietic stem-cell ageing. Nature 503, 392-396 (2013).
3. Geiger, H., De Haan, G. & Florian, M. C. The ageing haematopoietic stem cell compartment. Nat. Rev. Immunol. 13, 376-389 (2013).
4. Morrison, S. J., Wandycz, A. M., Akashi, K., Globerson, A. & Weissman, I. L. The aging of hematopoietic stem cells. Nat. Med. 2, 1011-1016 (1996).
5. Dykstra, B., Olthof, S., Schreuder, J., Ritsema, M. & De Haan, G. Clonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells. J. Exp. Med. 208, 2691-2703 (2011).
6. Sudo, K., Ema, H., Morita, Y. & Nakauchi, H. Age-associated characteristics of murine hematopoietic stem cells. J. Exp. Med. 192, 1273-1280 (2000).
7. Pang, W. W. et al. Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age. Proc. Natl Acad. Sci. USA 108, 20012-20017 (2011).
8. Beerman, I. et al. Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion. Proc. Natl Acad. Sci. USA 107, 5465-5470 (2010).
9. Cho, R. H., Sieburg, H. B. & Muller-Sieburg, C. E. A new mechanism for the aging of hematopoietic stem cells: Aging changes the clonal composition of the stem cell compartment but not individual stem cells. Blood 111, 5553-5561 (2008).
10. Montecino-Rodriguez, E., Berent-Maoz, B. & Dorshkind, K. Causes, consequences, and reversal of immune system aging. J. Clin. Invest. 123, 958-965 (2013).
11. Morita, Y., Ema, H. & Nakauchi, H. Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment. J. Exp. Med. 207, 1173-1182 (2010).
12. Ito, K. et al. Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells. Nature 431, 997-1002 (2004).
13. Janzen, V. et al. Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. Nature 443, 421-426 (2006).
14. Maryanovich, M. et al. The ATM-BID pathway regulates quiescence and survival of haematopoietic stem cells. Nat. Cell Biol. 14, 535-541 (2012).
15. Pant, V., Quintas-Cardama, A. & Lozano, G. The p53 pathway in hematopoiesis: Lessons from mouse models, implications for humans. Blood 120, 5118-5127 (2012).
16. Shao, L. et al. Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a-and Arf-independent manner. Blood 123, 3105-3115 (2014).
17. Wang, J. et al. A differentiation checkpoint limits hematopoietic stem cell self-renewal in response to DNA damage. Cell 148, 1001-1014 (2012).
18. Lowe, J. et al. Regulation of the Wip1 phosphatase and its effects on the stress response. Front. Biosci. 17, 1480-1498 (2012).
19. Lu, X. et al. The type 2C phosphatase Wip1: An oncogenic regulator of tumor suppressor and DNA damage response pathways. Cancer Metastasis Rev. 27, 123-135 (2008).
20. Filipponi, D., Muller, J., Emelyanov, A. & Bulavin, D. V. Wip1 controls global heterochromatin silencing via ATM/BRCA1-dependent DNA methylation. Cancer cell 24, 528-541 (2013).
21. Demidov, O. N. et al. Wip1 phosphatase regulates p53-dependent apoptosis of stem cells and tumorigenesis in the mouse intestine. Cell Stem Cell 1, 180-190 (2007).
22. Bulavin, D. V. et al. Inactivation of the Wip1 phosphatase inhibits mammary tumorigenesis through p38 MAPK-mediated activation of the p16(Ink4a)-p19(Arf) pathway. Nat. Genet. 36, 343-350 (2004).
23. Zhu, Y. et al. Phosphatase WIP1 regulates adult neurogenesis and WNT signaling during aging. J. Clin. Invest. 124, 3263-3273 (2014).
24. Zhu, Y. H. et al. Wip1 regulates the generation of new neural cells in the adult olfactory bulb through p53-dependent cell cycle control. Stem Cells 27, 1433-1442 (2009).
25. Le Guezennec, X. et al. Wip1-dependent regulation of autophagy, obesity, and atherosclerosis. Cell Metab. 16, 68-80 (2012).
26. Wong, E. S. et al. p38MAPK controls expression of multiple cell cycle inhibitors and islet proliferation with advancing age. Dev. Cell 17, 142-149 (2009).
27. Choi, J. et al. Mice deficient for the wild-type p53-induced phosphatase gene (Wip1) exhibit defects in reproductive organs, immune function, and cell cycle control. Mol. Cell Biol. 22, 1094-1105 (2002).
28. Schito, M. L., Demidov, O. N., Saito, S., Ashwell, J. D. & Appella, E. Wip1 phosphatase-deficient mice exhibit defective T cell maturation due to sustained p53 activation. J. Immunol. 176, 4818-4825 (2006).
29. Liu, G. et al. Phosphatase Wip1 negatively regulates neutrophil development through p38 MAPK-STAT1. Blood 121, 519-529 (2013).
30. Verovskaya, E. et al. Heterogeneity of young and aged murine hematopoietic stem cells revealed by quantitative clonal analysis using cellular barcoding. Blood 122, 523-532 (2013).
31. Dumble, M. et al. The impact of altered p53 dosage on hematopoietic stem cell dynamics during aging. Blood 109, 1736-1742 (2007).
32. Liu, Y. et al. p53 regulates hematopoietic stem cell quiescence. Cell Stem Cell 4, 37-48 (2009).
33. Cheng, T. et al. Hematopoietic stem cell quiescence maintained by p21cip1/waf1. Science 287, 1804-1808 (2000).
34. Frelin, C. et al. GATA-3 regulates the self-renewal of long-term hematopoietic stem cells. Nat. Immunol. 14, 1037-1044 (2013).
35. Stein, S. J. & Baldwin, A. S. Deletion of the NF-kappaB subunit p65/RelA in the hematopoietic compartment leads to defects in hematopoietic stem cell function. Blood 121, 5015-5024 (2013).
36. Chen, C. et al. TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species. J. Exp. Med. 205, 2397-2408 (2008).
37. Chew, J. et al. WIP1 phosphatase is a negative regulator of NF-kappaB signalling. Nat. Cell Biol. 11, 659-666 (2009).
38. Choudhury, A. R. et al. Cdkn1a deletion improves stem cell function and lifespan of mice with dysfunctional telomeres without accelerating cancer formation. Nat. Genet. 39, 99-105 (2007).
39. Tyner, S. D. et al. p53 mutant mice that display early ageing-associated phenotypes. Nature 415, 45-53 (2002).
40. Garcia-Cao, I. et al. Increased p53 activity does not accelerate telomere-driven ageing. EMBO Rep. 7, 546-552 (2006).
41. Yu, W. M. et al. Metabolic regulation by the mitochondrial phosphatase PTPMT1 is required for hematopoietic stem cell differentiation. Cell Stem Cell 12, 62-74 (2013).
42. Challen, G. A. et al. Dnmt3a is essential for hematopoietic stem cell differentiation. Nat. Genet. 44, 23-31 (2012).
43. Sun, D. et al. Epigenomic profiling of young and aged HSCs reveals concerted changes during aging that reinforce self-renewal. Cell Stem Cell 14, 673-688 (2014).
44. Ceccaldi, R. et al. Bone marrow failure in Fanconi anemia is triggered by an exacerbated p53/p21 DNA damage response that impairs hematopoietic stem and progenitor cells. Cell Stem Cell 11, 36-49 (2012).
45. Chen, C., Liu, Y., Liu, Y. & Zheng, P. mTOR regulation and therapeutic rejuvenation of aging hematopoietic stem cells. Sci. Signal. 2, ra75 (2009).
46. Gan, B. et al. mTORC1-dependent and-independent regulation of stem cell renewal, differentiation, and mobilization. Proc. Natl Acad. Sci. USA 105, 19384-19389 (2008).
47. Yilmaz, O. H. et al. Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells. Nature 441, 475-482 (2006).
48. Zhang, J. et al. PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention. Nature 441, 518-522 (2006).
49. Gilmartin, A. G. et al. Allosteric Wip1 phosphatase inhibition through flap-subdomain interaction. Nat. Chem. Biol. 10, 181-187 (2014).
50. Hidalgo, I. et al. Ezh1 is required for hematopoietic stem cell maintenance and prevents senescence-like cell cycle arrest. Cell Stem Cell 11, 649-662 (2012).