Hematopoietic stem cells are acutely sensitive to Acd shelterin gene inactivation

Journal of Clinical Investigation

Volumn 124, Issue 1, 2014, Pages 353-366

  Jones, Morgan ^a,b,c   Osawa, Gail ^d   Regal, Joshua A ^c,e   Weinberg, Daniel N ^a   Taggart, James ^a   Kocak, Hande ^f   Friedman, Ann ^a   Ferguson, David O ^e   Keegan, Catherine E ^d,f   Maillard, Ivan ^a,e,g  

^a Life Sciences Institute   (United States)

^b Program in Cell and Molecular Biology   (United States)

^c Medical Scientist Training Program   (United States)

^d UNIVERSITY OF MICHIGAN HEALTH SYSTEM   (United States)

^e UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^f Department of Human Genetics ^*  (United States)

^g Division of Hematology Oncology 3216 Cancer Center   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEIN; PROTEIN P53; TPP1 PROTEIN; UNCLASSIFIED DRUG;

ACD GENE; ALLELE; ANIMAL CELL; ARTICLE; BONE MARROW CELL; CELL ASSAY; CELL CYCLE ARREST; CELL FUNCTION; CELL FUSION; CONTROLLED STUDY; FETUS; FETUS LIVER; GENE; GENE EXPRESSION; GENE INACTIVATION; HEMATOPOIETIC STEM CELL; HOMOZYGOSITY; MOUSE; NONHUMAN; PRIORITY JOURNAL; TELOMERE SHORTENING;

EID: 84892922281     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI67871     Document Type: Article

References (66)

1. Greenberg RA, Allsopp RC, Chin L, Morin GB, Depinho RA. Expression of mouse telomerase reverse transcriptase during development, differentiation and proliferation. Oncogene. 1998;16(13):1723-1730
2. Breault DT, et al. Generation of mTert-GFP mice as a model to identify and study tissue progenitor cells. Proc Natl Acad Sci U S A. 2008;105(30):10420-10425
3. Lee HW, et al. Essential role of mouse telomerase in highly proliferative organs. Nature. 1998;392(6676):569-574
4. Palm W, De Lange T. How shelterin protects mammalian telomeres. Annu Rev Genet. 2008;42:301-334
5. Denchi EL, De Lange T. Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1. Nature. 2007;448(7157):1068-1071
6. Guo X, et al. Dysfunctional telomeres activate an ATM-ATR-dependent DNA damage response to suppress tumorigenesis. EMBO J. 2007; 26(22):4709-4719
7. Hockemeyer D, et al. Telomere protection by mammalian Pot1 requires interaction with Tpp1. Nat Struct Mol Biol. 2007;14(8):754-761
8. Kibe T, Osawa GA, Keegan CE, De Lange T. Telomere protection by TPP1 is mediated by POT1a and POT1b. Mol Cell Biol. 2010;30(4):1059-1066
9. Wang F, et al. The POT1-TPP1 telomere complex is a telomerase processivity factor. Nature. 2007; 445(7127):506-510
10. Xin H, et al. TPP1 is a homologue of ciliate TEBP- beta and interacts with POT1 to recruit telomerase. Nature. 2007;445(7127):559-562
11. Chong L, et al. A human telomeric protein. Science. 1995;270(5242):1663- 1667
12. Bilaud T, Brun C, Ancelin K, Koering CE, Laroche T, Gilson E. Telomeric localization of TRF2, a novel human telobox protein. Nat Genet. 1997; 17(2):236-239
13. Broccoli D, Smogorzewska A, Chong L, De Lange T. Human telomeres contain two distinct Myb-related proteins, TRF1 and TRF2. Nat Genet. 1997; 17(2):231-235
14. Smogorzewska A, De Lange T. Different telomere damage signaling pathways in human and mouse cells. EMBO J. 2002;21(16):4338-4348
15. Ye JZ, et al. TIN2 binds TRF1 and TRF2 simultaneously and stabilizes the TRF2 complex on telomeres. J Biol Chem. 2004;279(45):47264-47271
16. Takai KK, Kibe T, Donigian JR, Frescas D, De Lange T. Telomere protection by TPP1/POT1 requires tethering to TIN2. Mol Cell. 2011;44(4):647-659
17. Pardo B, Marcand S. Rap1 prevents telomere fusions by nonhomologous end joining. EMBO J. 2005; 24(17):3117-3127
18. Bae NS, Baumann P. A RAP1/TRF2 complex inhibits nonhomologous end-joining at human telomeric DNA ends. Mol Cell. 2007;26(3):323-334
19. Sarthy J, Bae NS, Scrafford J, Baumann P. Human RAP1 inhibits non-homologous end joining at telomeres. EMBO J. 2009;28(21):3390-3399
20. Hockemeyer D, Daniels JP, Takai H, De Lange T. Recent expansion of the telomeric complex in rodents: Two distinct POT1 proteins protect mouse telomeres. Cell. 2006;126(1):63-77
21. Palm W, Hockemeyer D, Kibe T, De Lange T. Functional dissection of human and mouse POT1 proteins. Mol Cell Biol. 2009;29(2):471-482
22. He H, et al. Pot1b deletion and telomerase haploinsufficiency in mice initiate an ATR-dependent DNA damage response and elicit phenotypes resembling dyskeratosis congenita. Mol Cell Biol. 2009; 29(1):229-240
23. Calado RT, Young NS. Telomere diseases. N Engl J Med. 2009;361(24):2353-2365
24. Savage SA, Calado RT, Xin ZT, Ly H, Young NS, Chanock SJ. Genetic variation in telomeric repeat binding factors 1 and 2 in aplastic anemia. Exp Hematol. 2006;34(5):664-671
25. Walne AJ, Vulliamy T, Beswick R, Kirwan M, Dokal I. TINF2 mutations result in very short telomeres: analysis of a large cohort of patients with dyskeratosis congenita and related bone marrow failure syndromes. Blood. 2008;112(9):3594-3600
26. Savage SA, Giri N, Baerlocher GM, Orr N, Lansdorp PM, Alter BP. TINF2, a component of the shelterin telomere protection complex, is mutated in dyskeratosis congenita. Am J Hum Genet. 2008; 82(2):501-509
27. Sarper N, Zengin E, Kilic SC. A child with severe form of dyskeratosis congenita and TINF2 mutation of shelterin complex. Pediatr Blood Cancer. 2010; 55(6):1185-1186
28. Vulliamy TJ, et al. Differences in disease severity but similar telomere lengths in genetic subgroups of patients with telomerase and shelterin mutations. PLoS One. 2011;6(9):e24383
29. Vulliamy T, Beswick R, Kirwan MJ, Hossain U, Walne AJ, Dokal I. Telomere length measurement can distinguish pathogenic from non-pathogenic variants in the shelterin component, TIN2. Clin Genet. 2012;81(1):76-81
30. Keegan CE, et al. Urogenital and caudal dysgenesis in adrenocortical dysplasia (acd) mice is caused by a splicing mutation in a novel telomeric regulator. Hum Mol Genet. 2005;14(1):113-123
31. Tejera AM, et al. TPP1 is required for TERT recruitment, telomere elongation during nuclear reprogramming, and normal skin development in mice. Dev Cell. 2010;18(5):775-789
32. Vlangos CN, O'Connor BC, Morley MJ, Krause AS, Osawa GA, Keegan CE. Caudal regression in adrenocortical dysplasia (acd) mice is caused by telomere dysfunction with subsequent p53-dependent apoptosis. Dev Biol. 2009;334(2):418-428
33. Else T, et al. Genetic p53 deficiency partially rescues the adrenocortical dysplasia phenotype at the expense of increased tumorigenesis. Cancer Cell. 2009;15(6):465-476
34. Wang Y, Shen MF, Chang S. Essential roles for Pot1b in HSC self-renewal and survival. Blood. 2011;118(23):6068-6077
35. Else T, et al. Tpp1/Acd maintains genomic stability through a complex role in telomere protection. Chromosome Res. 2007;15(8):1001-1013
36. Kiel MJ, Yilmaz OH, Iwashita T, Yilmaz OH, Terhorst C, Morrison SJ. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell. 2005; 121(7):1109-1121
37. Kim I, He S, Yilmaz OH, Kiel MJ, Morrison SJ. Enhanced purification of fetal liver hematopoietic stem cells using SLAM family receptors. Blood. 2006; 108(2):737-744
38. Kuhn R, Schwenk F, Aguet M, Rajewsky K. Inducible gene targeting in mice. Science. 1995; 269(5229):1427-1429
39. Essers MA, et al. IFNá activates dormant haematopoietic stem cells in vivo. Nature. 2009; 458(7240):904-908
40. Ruzankina Y, et al. Deletion of the developmentally essential gene ATR in adult mice leads to age-related phenotypes and stem cell loss. Cell Stem Cell. 2007; 1(1):113-126
41. Chen MJ, Yokomizo T, Zeigler BM, Dzierzak E, Speck NA. Runx1 is required for the endothelial to haematopoietic cell transition but not thereafter. Nature. 2009;457(7231):887-891
42. Stadtfeld M, Graf T. Assessing the role of hematopoietic plasticity for endothelial and hepatocyte development by non-invasive lineage tracing. Development. 2005;132(1):203-213
43. Warr MR, et al. FOXO3A directs a protective autophagy program in haematopoietic stem cells. Nature. 2013;494(7437):323-327
44. Scaffidi P, Misteli T, Bianchi ME. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature. 2002;418(6894):191-195
45. Sahin E, et al. Telomere dysfunction induces metabolic and mitochondrial compromise. Nature. 2011; 470(7334):359-365
46. Chen LY, et al. Mitochondrial localization of telomeric protein TIN2 links telomere regulation to metabolic control. Mol Cell. 2012;47(6):839-850
47. Castedo M, Perfettini JL, Roumier T, Andreau K, Medema R, Kroemer G. Cell death by mitotic catastrophe: a molecular definition. Oncogene. 2004; 23(16):2825-2837
48. Castedo M, et al. Mitotic catastrophe constitutes a special case of apoptosis whose suppression entails aneuploidy. Oncogene. 2004;23(25):4362-4370
49. Micheau O, Tschopp J. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell. 2003;114(2):181-190
50. Micheau O, et al. The long form of FLIP is an activator of caspase-8 at the Fas death-inducing signaling complex. J Biol Chem. 2002;277(47):45162-45171
51. Tait SW, Green DR. Mitochondria and cell death: outer membrane permeabilization and beyond. Nat Rev Mol Cell Biol. 2010;11(9):621-632
52. Thanasoula M, et al. p53 prevents entry into mitosis with uncapped telomeres. Curr Biol. 2010; 20(6):521-526
53. Cosme-Blanco W, et al. Telomere dysfunction suppresses spontaneous tumorigenesis in vivo by initiating p53-dependent cellular senescence. EMBO Rep. 2007;8(5):497-503
54. D'adda Di Fagagna F, et al. A DNA damage checkpoint response in telomere-initiated senescence. Nature. 2003;426(6963):194-198
55. Herbig U, Jobling WA, Chen BP, Chen DJ, Sedivy JM. Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). Mol Cell. 2004; 14(4):501-513
56. Hockemeyer D, Palm W, Wang RC, Couto SS, De Lange T. Engineered telomere degradation models dyskeratosis congenita. Genes Dev. 2008; 22(13):1773-1785
57. Ballew BJ, Savage SA. Updates on the biology and management of dyskeratosis congenita and related telomere biology disorders. Expert Rev Hematol. 2013;6(3):327-337
58. Savage SA, Alter BP. Dyskeratosis congenita. Hematol Oncol Clin North Am. 2009;23(2):215-231
59. Nandakumar J, Bell CF, Weidenfeld I, Zaug AJ, Leinwand LA, Cech TR. The TEL patch of telomere protein TPP1 mediates telomerase recruitment and processivity. Nature. 2012;492(7428):285-289
60. Zhong FL, Batista LF, Freund A, Pech MF, Venteicher AS, Artandi SE. TPP1 OB-fold domain controls telomere maintenance by recruiting telomerase to chromosome ends. Cell. 2012; 150(3):481-494
61. Beier F, Foronda M, Martinez P, Blasco MA. Conditional TRF1 knockout in the hematopoietic compartment leads to bone marrow failure and recapitulates clinical features of Dyskeratosis congenita. Blood. 2012;120(15):2990-3000
62. De Boer J, et al. Transgenic mice with hematopoietic and lymphoid specific expression of Cre. Eur J Immunol. 2003;33(2):314-325
63. Jacks T, et al. Tumor spectrum analysis in p53-mutant mice. Curr Biol. 1994;4(1):1-7
64. Cawthon RM. Telomere measurement by quantitative PCR. Nucleic Acids Res. 2002;30(10):e47
65. Callicott RJ, Womack JE. Real-time PCR assay for measurement of mouse telomeres. Comp Med. 2006; 56(1):17-22
66. Lansdorp PM, et al. Heterogeneity in telomere length of human chromosomes. Hum Mol Genet. 1996;5(5):685-691.