Biased competition between Lgr5 intestinal stem cells driven by oncogenic mutation induces clonal expansion

EMBO Reports

Volumn 15, Issue 1, 2014, Pages 62-69

  Snippert, Hugo J ^a   Schepers, Arnout G ^a,b   Van Es, Johan H ^a   Simons, Benjamin D ^c,d,e   Clevers, Hans ^a  

^a UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

^b MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^c UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^d UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^e UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

Crypt fission; Field cancerization; K ras; Lgr5 intestinal stem cells; Neutral competition

Indexed keywords

G PROTEIN COUPLED RECEPTOR; KRAS2 PROTEIN, MOUSE; LGR5 PROTEIN, MOUSE; PROTEIN P21;

ADULT STEM CELL; ANIMAL; CELL CYCLE; CELL PROLIFERATION; CELL TRANSFORMATION; COLORECTAL TUMOR; GENETICS; INTESTINE MUCOSA; METABOLISM; MISSENSE MUTATION; MOUSE; ONCOGENE; PATHOLOGY; PHYSIOLOGY; SMALL INTESTINE; STEM CELL NICHE; TRANSGENIC MOUSE;

ADULT STEM CELLS; ANIMALS; CELL CYCLE; CELL PROLIFERATION; CELL TRANSFORMATION, NEOPLASTIC; COLORECTAL NEOPLASMS; INTESTINAL MUCOSA; INTESTINE, SMALL; MICE; MICE, TRANSGENIC; MUTATION, MISSENSE; ONCOGENES; PROTO-ONCOGENE PROTEINS P21(RAS); RECEPTORS, G-PROTEIN-COUPLED; STEM CELL NICHE;

EID: 84894541975     PISSN: 1469221X     EISSN: 14693178     Source Type: Journal    
DOI: 10.1002/embr.201337799     Document Type: Article

References (35)

1. Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61: 759-767
2. Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AM, Bos JL (1988) Genetic alterations during colorectal-tumor development. N Engl J Med 319: 525-532
3. Aivado M, Gynes M, Gorelov V, Schmidt WU, Roher HD, Goretzki PE (2000) ["Field cancerization"-an additional phenomenon in development of colon tumors? K-ras codon 12 mutations in normal colonic mucosa of patients with colorectal neoplasms]. Chirurg 71: 1230-1234; discussion 1234-1235
4. Zhu D, Keohavong P, Finkelstein SD, Swalsky P, Bakker A, Weissfeld J, Srivastava S, Whiteside TL (1997) K-ras gene mutations in normal colorectal tissues from K-ras mutation-positive colorectal cancer patients. Cancer Res 57: 2485-2492
5. Baker AM, Graham TA, Wright NA (2013) Pre-tumour clones, periodic selection and clonal interference in the origin and progression of gastro-intestinal cancer: potential for biomarker development. J Pathol 229: 502-514
6. van der Flier LG, Clevers H (2009) Stem cells, self-renewal, and differentiation in the intestinal epithelium. Annu Rev Physiol 71: 241-260
7. Snippert HJ, van der Flier LG, Sato T, van Es JH, van den Born M, Kroon-Veenboer C, Barker N, Klein AM, van Rheenen J, Simons BD, Clevers H (2010) Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells. Cell 143: 134-144
8. Sato T, van Es JH, Snippert HJ, Stange DE, Vries RG, van den Born M, Barker N, Shroyer NF, van de Wetering M, Clevers H (2011) Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature 469: 415-418
9. Farin HF, Van Es JH, Clevers H (2012) Redundant sources of Wnt regulate intestinal stem cells and promote formation of Paneth cells. Gastroenterology 143: 1518-1529 e1517
10. Lopez-Garcia C, Klein AM, Simons BD, Winton DJ (2010) Intestinal stem cell replacement follows a pattern of neutral drift. Science 330: 822-825
11. Barker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H, van den Born M, Danenberg E, Clarke AR, Sansom OJ, Clevers H (2009) Crypt stem cells as the cells-of-origin of intestinal cancer. Nature 457: 608-611
12. Zhu L, Gibson P, Currle DS, Tong Y, Richardson RJ, Bayazitov IT, Poppleton H, Zakharenko S, Ellison DW, Gilbertson RJ (2009) Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation. Nature 457: 603-607
13. Schepers AG, Snippert HJ, Stange DE, van den Born M, van Es JH, van de Wetering M, Clevers H (2012) Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas. Science 337: 730-735
14. Haigis KM, Kendall KR, Wang Y, Cheung A, Haigis MC, Glickman JN, Niwa-Kawakita M, Sweet-Cordero A, Sebolt-Leopold J, Shannon KM, Settleman J, Giovannini M, Jacks T (2008) Differential effects of oncogenic K-Ras and N-Ras on proliferation, differentiation and tumor progression in the colon. Nat Genet 40: 600-608
15. Trobridge P, Knoblaugh S, Washington MK, Munoz NM, Tsuchiya KD, Rojas A, Song X, Ulrich CM, Sasazuki T, Shirasawa S, Grady WM (2009) TGF-beta receptor inactivation and mutant Kras induce intestinal neoplasms in mice via a beta-catenin-independent pathway. Gastroenterology 136: 1680-1688 e1687
16. Sansom OJ, Meniel V, Wilkins JA, Cole AM, Oien KA, Marsh V, Jamieson TJ, Guerra C, Ashton GH, Barbacid M, Clarke AR (2006) Loss of Apc allows phenotypic manifestation of the transforming properties of an endogenous K-ras oncogene in vivo. Proc Natl Acad Sci USA 103: 14122-14127
17. Ray KC, Bell KM, Yan J, Gu G, Chung CH, Washington MK, Means AL (2011) Epithelial tissues have varying degrees of susceptibility to Kras (G12D)-initiated tumorigenesis in a mouse model. PLoS One 6: e16786
18. Luo F, Brooks DG, Ye H, Hamoudi R, Poulogiannis G, Patek CE, Winton DJ, Arends MJ (2007) Conditional expression of mutated K-ras accelerates intestinal tumorigenesis in Msh2-deficient mice. Oncogene 26: 4415-4427
19. Slaughter DP, Southwick HW, Smejkal W (1953) Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer 6: 963-968
20. Braakhuis BJ, Tabor MP, Kummer JA, Leemans CR, Brakenhoff RH (2003) A genetic explanation of Slaughter's concept of field cancerization: evidence and clinical implications. Cancer Res 63: 1727-1730
21. Graham TA, McDonald SA, Wright NA (2011) Field cancerization in the GI tract. Future Oncol 7: 981-993
22. Kozar S, Morrissey E, Nicholson AM, van der Heijden M, Zecchini HI, Kemp R, Tavare S, Vermeulen L, Winton DJ (2013) Continuous clonal labeling reveals small numbers of functional stem cells in intestinal crypts and adenomas. Cell Stem Cell 13: 626-633
23. Schepers AG, Vries R, van den Born M, van de Wetering M, Clevers H (2011) Lgr5 intestinal stem cells have high telomerase activity and randomly segregate their chromosomes. EMBO J 30: 1104-1109
24. Marshman E, Booth C, Potten CS (2002) The intestinal epithelial stem cell. Bioessays 24: 91-98
25. Totafurno J, Bjerknes M, Cheng H (1987) The crypt cycle. Crypt and villus production in the adult intestinal epithelium. Biophys J 52: 279-294
26. Park HS, Goodlad RA, Wright NA (1995) Crypt fission in the small intestine and colon. A mechanism for the emergence of G6PD locus-mutated crypts after treatment with mutagens. Am J Pathol 147: 1416-1427
27. Bjerknes M (1995) The crypt cycle and the asymptotic dynamics of the proportion of differently sized mutant crypt clones in the mouse intestine. Proc Biol Sci 260: 1-6
28. Bjerknes M (1996) Expansion of mutant stem cell populations in the human colon. J Theor Biol 178: 381-385
29. Bjerknes M (1986) A test of the stochastic theory of stem cell differentiation. Biophys J 49: 1223-1227
30. Greaves LC, Preston SL, Tadrous PJ, Taylor RW, Barron MJ, Oukrif D, Leedham SJ, Deheragoda M, Sasieni P, Novelli MR, Jankowski JA, Turnbull DM, Wright NA, McDonald SA (2006) Mitochondrial DNA mutations are established in human colonic stem cells, and mutated clones expand by crypt fission. Proc Natl Acad Sci USA 103: 714-719
31. Feng Y, Bommer GT, Zhao J, Green M, Sands E, Zhai Y, Brown K, Burberry A, Cho KR, Fearon ER (2011) Mutant KRAS promotes hyperplasia and alters differentiation in the colon epithelium but does not expand the presumptive stem cell pool. Gastroenterology 141: 1003-1013 e1001-1010
32. Wong WM, Mandir N, Goodlad RA, Wong BC, Garcia SB, Lam SK, Wright NA (2002) Histogenesis of human colorectal adenomas and hyperplastic polyps: the role of cell proliferation and crypt fission. Gut 50: 212-217
33. Schwitalla S, Fingerle AA, Cammareri P, Nebelsiek T, Goktuna SI, Ziegler PK, Canli O, Heijmans J, Huels DJ, Moreaux G, Rupec RA, Gerhard M, Schmid R, Barker N, Clevers H, Lang R, Neumann J, Kirchner T, Taketo MM, van den Brink GR, et al. (2013) Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties. Cell 152: 25-38
34. Thirlwell C, Will OC, Domingo E, Graham TA, McDonald SA, Oukrif D, Jeffrey R, Gorman M, Rodriguez-Justo M, Chin-Aleong J, Clark SK, Novelli MR, Jankowski JA, Wright NA, Tomlinson IP, Leedham SJ (2010) Clonality assessment and clonal ordering of individual neoplastic crypts shows polyclonality of colorectal adenomas. Gastroenterology 138: 1441-1454, 1454 e1441-1447
35. Nosho K, Kure S, Irahara N, Shima K, Baba Y, Spiegelman D, Meyerhardt JA, Giovannucci EL, Fuchs CS, Ogino S (2009) A prospective cohort study shows unique epigenetic, genetic, and prognostic features of synchronous colorectal cancers. Gastroenterology 137: 1609-1620 e1601-1603