Reserve stem cells: Differentiated cells reprogram to fuel repair, metaplasia, and neoplasia in the adult gastrointestinal tract

Science Signaling

Volumn 8, Issue 385, 2015, Pages

  Mills, Jason C ^a   Sansom, Owen J ^b  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b BEATSON INSTITUTE FOR CANCER RESEARCH   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

APC PROTEIN; CRE RECOMBINASE; CYCLIN DEPENDENT KINASE INHIBITOR 2A; HEPATOCYTE NUCLEAR FACTOR 1; K RAS PROTEIN; MAMMALIAN TARGET OF RAPAMYCIN; MUCIN 6; RAC1 PROTEIN; REACTIVE OXYGEN METABOLITE; TRANSCRIPTION FACTOR PDX 1; X BOX BINDING PROTEIN 1; TRANSCRIPTION FACTOR;

ADULT STEM CELL; APOPTOSIS; CELL DEDIFFERENTIATION; CELL DIFFERENTIATION; CELL PROLIFERATION; CELL TRANSDIFFERENTIATION; DIGESTIVE SYSTEM CANCER; GENE MUTATION; HUMAN; INTESTINE; INTESTINE CANCER; INTESTINE METAPLASIA; METAPLASIA; NONHUMAN; PANCREAS CANCER; PANCREATITIS; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; STOMACH; STOMACH CANCER; STOMACH METAPLASIA; ANIMAL; CELL LINEAGE; CYTOLOGY; GASTROINTESTINAL TRACT; METABOLISM; MITOSIS; NEOPLASM; NUCLEAR REPROGRAMMING; PANCREAS; PATHOLOGY; REGENERATION; STEM CELL;

ANIMALS; APOPTOSIS; CELL DIFFERENTIATION; CELL LINEAGE; CELLULAR REPROGRAMMING; GASTROINTESTINAL TRACT; HUMANS; INTESTINES; MITOSIS; NEOPLASMS; PANCREAS; REGENERATION; STEM CELLS; STOMACH; TRANSCRIPTION FACTORS;

EID: 84937574058     PISSN: 19450877     EISSN: 19379145     Source Type: Journal    
DOI: 10.1126/scisignal.aaa7540     Document Type: Review

References (162)

1. C. H. Waddington, The Strategy of the Genes. A Discussion of Some Aspects of Theoretical Biology (George Allen & Unwin, London, 1957).
2. E. D. Hay, The fine structure of blastema cells and differentiating cartilage cells in regenerating limbs of Amblystoma larvae. J. Biophys. Biochem. Cytol. 4, 583-591 (1958).
3. V. S. Mashanov, O. R. Zueva, J. E. Garcia-Arraras, Expression of pluripotency factors in echinoderm regeneration. Cell Tissue Res. 359, 521-536 (2015).
4. C. Mosher, Observations on evisceration and visceral regeneration in the sea-cucumber, Actinopyga agassizi Selenka. Zoologica 41, 17-26 (1956).
5. D. Zipori, The stem state: Plasticity is essential, whereas self-renewal and hierarchy are optional. Stem Cells 23, 719-726 (2005).
6. K. Takahashi, K. Tanabe, M. Ohnuki, M. Narita, T. Ichisaka, K. Tomoda, S. Yamanaka, Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861-872 (2007).
7. K. Takahashi, S. Yamanaka, Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663-676 (2006).
8. K. Takahashi, S. Yamanaka, Induced pluripotent stem cells in medicine and biology. Development 140, 2457-2461 (2013).
9. L. C. Murtaugh, M. D. Keefe, Regeneration and repair of the exocrine pancreas. Annu. Rev. Plant. Physiol. Plant. Mol. Biol. 77, 229-249 (2015).
10. S. Puri, A. E. Folias, M. Hebrok, Plasticity and dedifferentiation within the pancreas: Development, homeostasis, and disease. Cell Stem Cell 16, 18-31 (2015).
11. D. A. Hess, S. E. Humphrey, J. Ishibashi, B. Damsz, A. H. Lee, L. H. Glimcher, S. F. Konieczny, Extensive pancreas regeneration following acinar-specific disruption of Xbp1 in mice. Gastroenterology 141, 1463-1472 (2011).
12. D. Direnzo, D. A. Hess, B. Damsz, J. E. Hallett, B. Marshall, C. Goswami, Y. Liu, T. Deering, R. J. Macdonald, S. F. Konieczny, Induced Mist1 expression promotes remodeling of mouse pancreatic acinar cells. Gastroenterology 143, 469-480 (2012).
13. C. L. Johnson, A. S. Kowalik, N. Rajakumar, C. L. Pin, Mist1 is necessary for the establishment of granule organization in serous exocrine cells of the gastrointestinal tract. Mech. Dev. 121, 261-272 (2004).
14. J. N. Jensen, E. Cameron, M. V. Garay, T. W. Starkey, R. Gianani, J. Jensen, Recapitulation of elements of embryonic development in adult mouse pancreatic regeneration. Gastroenterology 128, 728-741 (2005).
15. L. Zhu, G. Shi, C. M. Schmidt, R. H. Hruban, S. F. Konieczny, Acinar cells contribute to the molecular heterogeneity of pancreatic intraepithelial neoplasia. Am. J. Pathol. 171, 263-273 (2007).
16. O. J. De La, L. L. Emerson, J. L. Goodman, S. C. Froebe, B. E. Illum, A. B. Curtis, L. C. Murtaugh, Notch and Kras reprogram pancreatic acinar cells to ductal intraepithelial neoplasia. Proc. Natl. Acad. Sci. U.S.A. 105, 18907-18912 (2008).
17. N. Habbe, G. Shi, R. A. Meguid, V. Fendrich, F. Esni, H. Chen, G. Feldmann, D. A. Stoffers, S. F. Konieczny, S. D. Leach, A. Maitra, Spontaneous induction of murine pancreatic intraepithelial neoplasia (mPanIN) by acinar cell targeting of oncogenic Kras in adult mice. Proc. Natl. Acad. Sci. U.S.A. 105, 18913-18918 (2008).
18. G. Shi, D. DiRenzo, C. Qu, D. Barney, D. Miley, S. F. Konieczny, Maintenance of acinar cell organization is critical to preventing Kras-induced acinar-ductal metaplasia. Oncogene 32, 1950-1958 (2013).
19. A. E. Folias, C. Penaranda, A. L. Su, J. A. Bluestone, M. Hebrok, Aberrant innate immune activation following tissue injury impairs pancreatic regeneration. PLOS One 9, e102125 (2014).
20. J. L. Iovanna, P. Lechene de la Porte, J. C. Dagorn, Expression of genes associated with dedifferentiation and cell proliferation during pancreatic regeneration following acute pancreatitis. Pancreas 7, 712-718 (1992).
21. A. V. Pinho, I. Rooman, M. Reichert, N. De Medts, L. Bouwens, A. K. Rustgi, F. X. Real, Adult pancreatic acinar cells dedifferentiate to an embryonic progenitor phenotype with concomitant activation of a senescence programme that is present in chronic pancreatitis. Gut 60, 958-966 (2011).
22. L. Guo, M. D. Sans, Y. Hou, S. A. Ernst, J. A. Williams, c-Jun/AP-1 is required for CCK-induced pancreatic acinar cell dedifferentiation and DNA synthesis in vitro. Am. J. Physiol. Gastrointest. Liver Physiol. 302, G1381-G1396 (2012).
23. P. P. Prevot, A. Simion, A. Grimont, M. Colletti, A. Khalaileh, G. Van den Steen, C. Sempoux, X. Xu, V. Roelants, J. Hald, L. Bertrand, H. Heimberg, S. F. Konieczny, Y. Dor, F. P. Lemaigre, P. Jacquemin, Role of the ductal transcription factors HNF6 and Sox9 in pancreatic acinar-to-ductal metaplasia. Gut 61, 1723-1732 (2012).
24. J. L. Kopp, G. von Figura, E. Mayes, F. F. Liu, C. L. Dubois, J. P. Morris, F. C. Pan, H. Akiyama, C. V. Wright, K. Jensen, M. Hebrok, M. Sander, Identification of Sox9-dependent acinar-to-ductal reprogramming as the principal mechanism for initiation of pancreatic ductal adenocarcinoma. Cancer Cell 22, 737-750 (2012).
25. F. C. Pan, E. D. Bankaitis, D. Boyer, X. Xu, M. Van de Casteele, M. A. Magnuson, H. Heimberg, C. V. Wright, Spatiotemporal patterns of multipotentiality in Ptf1a-expressing cells during pancreas organogenesis and injury-induced facultative restoration. Development 140, 751-764 (2013).
26. K. E. Delgiorno, J. C. Hall, K. K. Takeuchi, F. C. Pan, C. J. Halbrook, M. K. Washington, K. P. Olive, J. R. Spence, B. Sipos, C. V. Wright, J. M. Wells, H. C. Crawford, Identification and manipulation of biliary metaplasia in pancreatic tumors. Gastroenterology 146, 233-244.e5 (2014).
27. P. P. Prevot, C. Augereau, A. Simion, G. Van den Steen, N. Dauguet, F. P. Lemaigre, P. Jacquemin, Let-7b and miR-495 stimulate differentiation and prevent metaplasia of pancreatic acinar cells by repressing HNF6. Gastroenterology 145, 668-678.e3 (2013).
28. P. Lechene de la Porte, J. Iovanna, C. Odaira, R. Choux, H. Sarles, Z. Berger, Involvement of tubular complexes in pancreatic regeneration after acute necrohemorrhagic pancreatitis. Pancreas 6, 298-306 (1991).
29. D. E. Bockman, W. R. Boydston, M. C. Anderson, Origin of tubular complexes in human chronic pancreatitis. Am. J. Surg. 144, 243-249 (1982).
30. I. Houbracken, E. de Waele, J. Lardon, Z. Ling, H. Heimberg, I. Rooman, L. Bouwens, Lineage tracing evidence for transdifferentiation of acinar to duct cells and plasticity of human pancreas. Gastroenterology 141, 731-741, 741.e1-741.e4 (2011).
31. M. A. Collins, W. Yan, J. S. Sebolt-Leopold, M. Pasca di Magliano, MAPK signaling is required for dedifferentiation of acinar cells and development of pancreatic intraepithelial neoplasia in mice. Gastroenterology 146, 822-834.e7 (2014).
32. R. L. Greer, B. K. Staley, A. Liou, M. Hebrok, Numb regulates acinar cell dedifferentiation and survival during pancreatic damage and acinar-to-ductal metaplasia. Gastroenterology 145, 1088-1097.e8 (2013).
33. C. Jhappan, C. Stahle, R. N. Harkins, N. Fausto, G. H. Smith, G. T. Merlino, TGFα overexpression in transgenic mice induces liver neoplasia and abnormal development of the mammary gland and pancreas. Cell 61, 1137-1146 (1990).
34. S. A. Blaine, K. C. Ray, R. Anunobi, M. A. Gannon, M. K. Washington, A. L. Means, Adult pancreatic acinar cells give rise to ducts but not endocrine cells in response to growth factor signaling. Development 137, 2289-2296 (2010).
35. Y. Dor, J. Brown, O. I. Martinez, D. A. Melton, Adult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation. Nature 429, 41-46 (2004).
36. M. M. Rankin, C. J. Wilbur, K. Rak, E. J. Shields, A. Granger, J. A. Kushner, β-Cells are not generated in pancreatic duct ligation-induced injury in adult mice. Diabetes 62, 1634-1645 (2013).
37. X. Xiao, Z. Chen, C. Shiota, K. Prasadan, P. Guo, Y. El-Gohary, J. Paredes, C. Welsh, J. Wiersch, G. K. Gittes, No evidence for β cell neogenesis in murine adult pancreas. J. Clin. Invest. 123, 2207-2217 (2013).
38. J. M. Bailey, J. Alsina, Z. A. Rasheed, F. M. McAllister, Y. Y. Fu, R. Plentz, H. Zhang, P. J. Pasricha, N. Bardeesy, W. Matsui, A. Maitra, S. D. Leach, DCLK1 marks a morphologically distinct subpopulation of cells with stem cell properties in preinvasive pancreatic cancer. Gastroenterology 146, 245-256 (2014).
39. F. Gerbe, B. Brulin, L. Makrini, C. Legraverend, P. Jay, DCAMKL-1 expression identifies Tuft cells rather than stem cells in the adult mouse intestinal epithelium. Gastroenterology 137, 2179-2180; author reply 2180-2181 (2009).
40. C. M. Ardito, B. M. Gruner, K. K. Takeuchi, C. Lubeseder-Martellato, N. Teichmann, P. K. Mazur, K. E. Delgiorno, E. S. Carpenter, C. J. Halbrook, J. C. Hall, D. Pal, T. Briel, A. Herner, M. Trajkovic-Arsic, B. Sipos, G. Y. Liou, P. Storz, N. R. Murray, D. W. Threadgill, M. Sibilia, M. K. Washington, C. L. Wilson, R. M. Schmid, E. W. Raines, H. C. Crawford, J. T. Siveke, EGF receptor is required for KRAS-induced pancreatic tumorigenesis. Cancer Cell 22, 304-317 (2012).
41. G. Y. Liou, H. Doppler, B. Necela, M. Krishna, H. C. Crawford, M. Raimondo, P. Storz, Macrophage-secreted cytokines drive pancreatic acinar-to-ductal metaplasia through NF-κB and MMPs. J. Cell Biol. 202, 563-577 (2013).
42. J. J. Hyun, H. S. Lee, Experimental models of pancreatitis. Clin. Endosc. 47, 212-216 (2014).
43. V. Zaninovic, A. S. Gukovskaya, I. Gukovsky, M. Mouria, S. J. Pandol, Cerulein upregulates ICAM-1 in pancreatic acinar cells, which mediates neutrophil adhesion to these cells. Am. J. Physiol. Gastrointest. Liver Physiol. 279, G666-G676 (2000).
44. S. Watanabe, K. Abe, Y. Anbo, H. Katoh, Changes in the mouse exocrine pancreas after pancreatic duct ligation: A qualitative and quantitative histological study. Arch. Histol. Cytol. 58, 365-374 (1995).
45. M. Baumgart, M. Werther, A. Bockholt, M. Scheurer, J. Ruschoff, W. Dietmaier, B. M. Ghadimi, E. Heinmoller, Genomic instability at both the base pair level and the chromosomal level is detectable in earliest PanIN lesions in tissues of chronic pancreatitis. Pancreas 39, 1093-1103 (2010).
46. G12D-induced pancreatic cancer development. Cancer Res. 70, 7114-7124 (2010).
47. G. Shi, L. Zhu, Y. Sun, R. Bettencourt, B. Damsz, R. H. Hruban, S. F. Konieczny, Loss of the acinar-restricted transcription factor Mist1 accelerates Kras-induced pancreatic intraepithelial neoplasia. Gastroenterology 136, 1368-1378 (2009).
48. C. Guerra, A. J. Schuhmacher, M. Canamero, P. J. Grippo, L. Verdaguer, L. Perez-Gallego, P. Dubus, E. P. Sandgren, M. Barbacid, Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice. Cancer Cell 11, 291-302 (2007).
49. D. A. Tuveson, S. R. Hingorani, Ductal pancreatic cancer in humans and mice. Cold Spring Harb. Symp. Quant. Biol. 70, 65-72 (2005).
50. R. H. Hruban, N. V. Adsay, J. Albores-Saavedra, M. R. Anver, A. V. Biankin, G. P. Boivin, E. E. Furth, T. Furukawa, A. Klein, D. S. Klimstra, G. Kloppel, G. Y. Lauwers, D. S. Longnecker, J. Luttges, A. Maitra, G. J. Offerhaus, L. Perez-Gallego, M. Redston, D. A. Tuveson, Pathology of genetically engineered mouse models of pancreatic exocrine cancer: Consensus report and recommendations. Cancer Res. 66, 95-106 (2006).
51. Y. Zhang, W. Yan, M. A. Collins, F. Bednar, S. Rakshit, B. R. Zetter, B. Z. Stanger, I. Chung, A. D. Rhim, M. P. di Magliano, Interleukin-6 is required for pancreatic cancer progression by promoting MAPK signaling activation and oxidative stress resistance. Cancer Res. 73, 6359-6374 (2013).
52. M. A. Collins, F. Bednar, Y. Zhang, J. C. Brisset, S. Galban, C. J. Galban, S. Rakshit, K. S. Flannagan, N. V. Adsay, M. Pasca di Magliano, Oncogenic Kras is required for both the initiation and maintenance of pancreatic cancer in mice. J. Clin. Invest. 122, 639-653 (2012).
53. C. Carriere, A. L. Young, J. R. Gunn, D. S. Longnecker, M. Korc, Acute pancreatitis markedly accelerates pancreatic cancer progression in mice expressing oncogenic Kras. Biochem. Biophys. Res. Commun. 382, 561-565 (2009).
54. H. Huang, J. Daniluk, Y. Liu, J. Chu, Z. Li, B. Ji, C. D. Logsdon, Oncogenic K-Ras requires activation for enhanced activity. Oncogene 33, 532-535 (2014).
55. J. Mallen-St Clair, R. Soydaner-Azeloglu, K. E. Lee, L. Taylor, A. Livanos, Y. Pylayeva-Gupta, G. Miller, R. Margueron, D. Reinberg, D. Bar-Sagi, EZH2 couples pancreatic regeneration to neoplastic progression. Genes Dev. 26, 439-444 (2012).
56. C. Guerra, M. Collado, C. Navas, A. J. Schuhmacher, I. Hernandez-Porras, M. Canamero, M. Rodriguez-Justo, M. Serrano, M. Barbacid, Pancreatitis-induced inflammation contributes to pancreatic cancer by inhibiting oncogene-induced senescence. Cancer Cell 19, 728-739 (2011).
57. E. P. Sandgren, N. C. Luetteke, R. D. Palmiter, R. L. Brinster, D. C. Lee, Overexpression of TGFα in transgenic mice: Induction of epithelial hyperplasia, pancreatic metaplasia, and carcinoma of the breast. Cell 61, 1121-1135 (1990).
58. E. T. Sawey, J. A. Johnson, H. C. Crawford, Matrix metalloproteinase 7 controls pancreatic acinar cell transdifferentiation by activating the Notch signaling pathway. Proc. Natl. Acad. Sci. U.S.A. 104, 19327-19332 (2007).
59. H. Ijichi, A. Chytil, A. E. Gorska, M. E. Aakre, Y. Fujitani, S. Fujitani, C. V. Wright, H. L. Moses, Aggressive pancreatic ductal adenocarcinoma in mice caused by pancreas-specific blockade of transforming growth factor-β signaling in cooperation with active Kras expression. Genes Dev. 20, 3147-3160 (2006).
60. E. P. Bottinger, J. L. Jakubczak, I. S. Roberts, M. Mumy, P. Hemmati, K. Bagnall, G. Merlino, L. M. Wakefield, Expression of a dominant-negative mutant TGF-β type II receptor in transgenic mice reveals essential roles for TGF-β in regulation of growth and differentiation in the exocrine pancreas. EMBO J. 16, 2621-2633 (1997).
61. T. Gao, D. Zhou, C. Yang, T. Singh, A. Penzo-Mendez, R. Maddipati, A. Tzatsos, N. Bardeesy, J. Avruch, B. Z. Stanger, Hippo signaling regulates differentiation and maintenance in the exocrine pancreas. Gastroenterology 144, 1543-1553.e1 (2013).
62. J. P. Morris, D. A. Cano, S. Sekine, S. C. Wang, M. Hebrok, β-Catenin blocks Kras-dependent reprogramming of acini into pancreatic cancer precursor lesions in mice. J. Clin. Invest. 120, 508-520 (2010).
63. A. Fukuda,. J. P. Morris, M. Hebrok, Bmi1 is required for regeneration of the exocrine pancreas in mice. Gastroenterology 143, 821-831.e2 (2012).
64. E. Sangiorgi, M. R. Capecchi, Bmi1 lineage tracing identifies a self-renewing pancreatic acinar cell subpopulation capable of maintaining pancreatic organ homeostasis. Proc. Natl. Acad. Sci. U.S.A. 106, 7101-7106 (2009).
65. J. C. Mills, P. H. Taghert, Scaling factors: Transcription factors regulating subcellular domains. Bioessays 34, 10-16 (2012).
66. + ductal cells are multipotent progenitors throughout development but do not produce new endocrine cells in the normal or injured adult pancreas. Development 138, 653-665 (2011).
67. S. M. Karam, C. P. Leblond, Dynamics of epithelial cells in the corpus of the mouse stomach. I. Identification of proliferative cell types and pinpointing of the stem cell. Anat. Rec. 236, 259-279 (1993).
68. S. M. Karam, C. P. Leblond, Dynamics of epithelial cells in the corpus of the mouse stomach. II. Outward migration of pit cells. Anat. Rec. 236, 280-296 (1993).
69. A. J. Bredemeyer, J. H. Geahlen, V. G. Weis, W. J. Huh, B. H. Zinselmeyer, S. Srivatsan, M. J. Miller, A. S. Shaw, J. C. Mills, The gastric epithelial progenitor cell niche and differentiation of the zymogenic (chief) cell lineage. Dev. Biol. 325, 211-224 (2009).
70. K. T. Nam, H. J. Lee, J. F. Sousa, V. G. Weis, R. L. O'Neal, P. E. Finke, J. Romero-Gallo, G. Shi, J. C. Mills, R. M. Peek Jr., S. F. Konieczny, J. R. Goldenring, Mature chief cells are cryptic progenitors for metaplasia in the stomach. Gastroenterology 139, 2028-2037.e9 (2010).
71. + chief cells act as reserve stem cells to generate all lineages of the stomach epithelium. Cell 155, 357-368 (2013).
72. Q. Li, S. M. Karam, J. I. Gordon, Diphtheria toxin-mediated ablation of parietal cells in the stomach of transgenic mice. J. Biol. Chem. 271, 3671-3676 (1996).
73. S. Nomura, H. Yamaguchi, M. Ogawa, T. C. Wang, J. R. Lee, J. R. Goldenring, Alterations in gastric mucosal lineages induced by acute oxyntic atrophy in wild-type and gastrin-deficient mice. Am. J. Physiol. Gastrointest. Liver Physiol. 288, G362-G375 (2005).
74. J. K. Lennerz, S. H. Kim, E. L. Oates, W. J. Huh, J. M. Doherty, X. Tian, A. J. Bredemeyer, J. R. Goldenring, G. Y. Lauwers, Y. K. Shin, J. C. Mills, The transcription factor MIST1 is a novel human gastric chief cell marker whose expression is lost in metaplasia, dysplasia, and carcinoma. Am. J. Pathol. 177, 1514-1533 (2010).
75. V. G. Ramsey, J. M. Doherty, C. C. Chen, T. S. Stappenbeck, S. F. Konieczny, J. C. Mills, The maturation of mucus-secreting gastric epithelial progenitors into digestive-enzyme secreting zymogenic cells requires Mist1. Development 134, 211-222 (2007).
76. S. M. Karam, Dynamics of epithelial cells in the corpus of the mouse stomach. IV. Bidirectional migration of parietal cells ending in their gradual degeneration and loss. Anat. Rec. 236, 314-332 (1993).
77. A. M. Hanby, R. Poulsom, R. J. Playford, N. A. Wright, The mucous neck cell in the human gastric corpus: A distinctive, functional cell lineage. J. Pathol. 187, 331-337 (1999).
78. J. H. Geahlen, C. Lapid, K. Thorell, I. Nikolskiy, W. J. Huh, E. L. Oates, J. K. Lennerz, X. Tian, V. G. Weis, S. S. Khurana, S. B. Lundin, A. R. Templeton, J. C. Mills, Evolution of the human gastrokine locus and confounding factors regarding the pseudogenicity of GKN3. Physiol. Genomics 45, 667-683 (2013).
79. T. R. Menheniott, A. J. Peterson, L. O'Connor, K. S. Lee, A. Kalantzis, I. Kondova, R. E. Bontrop, K. M. Bell, A. S. Giraud, A novel gastrokine, Gkn3, marks gastric atrophy and shows evidence of adaptive gene loss in humans. Gastroenterology 138, 1823-1835 (2010).
80. S. Nomura, T. Baxter, H. Yamaguchi, C. Leys, A. B. Vartapetian, J. G. Fox, J. R. Lee, T. C. Wang, J. R. Goldenring, Spasmolytic polypeptide expressing metaplasia to preneoplasia in H. felis-infected mice. Gastroenterology 127, 582-594 (2004).
81. J. R. Goldenring, K. T. Nam, J. C. Mills, The origin of pre-neoplastic metaplasia in the stomach: Chief cells emerge from the Mist. Exp. Cell Res. 317, 2759-2764 (2011).
82. B. J. Capoccia, R. U. Jin, Y. Y. Kong, R. M. Peek Jr., M. Fassan, M. Rugge, J. C. Mills, The ubiquitin ligase Mindbomb 1 coordinates gastrointestinal secretory cell maturation. J. Clin. Invest. 123, 1475-1491 (2013).
83. P. H. Schmidt, J. R. Lee, V. Joshi, R. J. Playford, R. Poulsom, N. A. Wright, J. R. Goldenring, Identification of a metaplastic cell lineage associated with human gastric adenocarcinoma. Lab. Invest. 79, 639-646 (1999).
84. I. Nookaew, K. Thorell, K. Worah, S. Wang, M. L. Hibberd, H. Sjovall, S. Pettersson, J. Nielsen, S. B. Lundin, Transcriptome signatures in Helicobacter pylori-infected mucosa identifies acidic mammalian chitinase loss as a corpus atrophy marker. BMC Med. Genomics 6, 41 (2013).
85. S. Nomura, S. H. Settle, C. M. Leys, A. L. Means, R. M. Peek Jr., S. D. Leach, C. V. Wright, R. J. Coffey, J. R. Goldenring, Evidence for repatterning of the gastric fundic epithelium associated with Ménétrier's disease and TGFα overexpression. Gastroenterology 128, 1292-1305 (2005).
86. L. I. Larsson, O. D. Madsen, P. Serup, J. Jonsson, H. Edlund, Pancreatic-duodenal homeobox 1-role in gastric endocrine patterning. Mech. Dev. 60, 175-184 (1996).
87. H. Sakai, Y. Eishi, X. L. Li, Y. Akiyama, S. Miyake, T. Takizawa, N. Konishi, M. Tatematsu, M. Koike, Y. Yuasa, PDX1 homeobox protein expression in pseudopyloric glands and gastric carcinomas. Gut 53, 323-330 (2004).
88. S. J. Henning, Postnatal development: Coordination of feeding, digestion, and metabolism. Am. J. Physiol. 241, G199-G214 (1981).
89. L. R. Johnson, Functional development of the stomach. Annu. Rev. Physiol. 47, 199-215 (1985).
90. S. M. Karam, Q. Li, J. I. Gordon, Gastric epithelial morphogenesis in normal and transgenic mice. Am. J. Physiol. 272, G1209-G1220 (1997).
91. L. H. Osaki, M. A. Curi, E. P. Alvares, P. Gama, Early weaning accelerates the differentiation of mucous neck cells in rat gastric mucosa: Possible role of TGFα/EGFR. Differentiation 79, 48-56 (2010).
92. T. M. Keeley, L. C. Samuelson, Cytodifferentiation of the postnatal mouse stomach in normal and Huntingtin-interacting protein 1-related-deficient mice. Am. J. Physiol. Gastrointest. Liver Physiol. 299, G1241-G1251 (2010).
93. K. Nozaki, M. Ogawa, J. A. Williams, B. J. Lafleur, V. Ng, R. I. Drapkin, J. C. Mills, S. F. Konieczny, S. Nomura, J. R. Goldenring, A molecular signature of gastric metaplasia arising in response to acute parietal cell loss. Gastroenterology 134, 511-522 (2008).
94. W. J. Huh, S. S. Khurana, J. H. Geahlen, K. Kohli, R. A. Waller, J. C. Mills, Tamoxifen induces rapid, reversible atrophy, and metaplasia in mouse stomach. Gastroenterology 142, 21-24.e7 (2012).
95. P. Correa, Human gastric carcinogenesis: A multistep and multifactorial process - First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res. 52, 6735-6740 (1992).
96. K. T. Nam, H. J. Lee, H. Mok, J. Romero-Gallo, J. E. Crowe Jr., R. M. Peek Jr., J. R. Goldenring, Amphiregulin-deficient mice develop spasmolytic polypeptide expressing metaplasia and intestinal metaplasia. Gastroenterology 136, 1288-1296 (2009).
97. J. R. Goldenring, K. T. Nam, T. C. Wang, J. C. Mills, N. A. Wright, Spasmolytic polypeptide-expressing metaplasia and intestinal metaplasia: Time for reevaluation of metaplasias and the origins of gastric cancer. Gastroenterology 138, 2207-2210.e1 (2010).
98. I. M. Toller, K. J. Neelsen, M. Steger, M. L. Hartung, M. O. Hottiger, M. Stucki, B. Kalali, M. Gerhard, A. A. Sartori, M. Lopes, A. Muller, Carcinogenic bacterial pathogen Helicobacter pylori triggers DNA double-strand breaks and a DNA damage response in its host cells. Proc. Natl. Acad. Sci. U.S.A. 108, 14944-14949 (2011).
99. Y. Matsumoto, H. Marusawa, K. Kinoshita, Y. Niwa, Y. Sakai, T. Chiba, Up-regulation of activation-induced cytidine deaminase causes genetic aberrations at the CDKN2b-CDKN2a in gastric cancer. Gastroenterology 139, 1984-1994 (2010).
100. A. M. Machado, C. Figueiredo, R. Seruca, L. J. Rasmussen, Helicobacter pylori infection generates genetic instability in gastric cells. Biochim. Biophys. Acta 1806, 58-65 (2010).
101. M. Umeda, N. Murata-Kamiya, Y. Saito, Y. Ohba, M. Takahashi, M. Hatakeyama, Helicobacter pylori CagA causes mitotic impairment and induces chromosomal instability. J. Biol. Chem. 284, 22166-22172 (2009).
102. Y. Matsumoto, H. Marusawa, K. Kinoshita, Y. Endo, T. Kou, T. Morisawa, T. Azuma, I. M. Okazaki, T. Honjo, T. Chiba, Helicobacter pylori infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium. Nat. Med. 13, 470-476 (2007).
103. S. A. McDonald, L. C. Greaves, L. Gutierrez-Gonzalez, M. Rodriguez-Justo, M. Deheragoda, S. J. Leedham, R. W. Taylor, C. Y. Lee, S. L. Preston, M. Lovell, T. Hunt, G. Elia, D. Oukrif, R. Harrison, M. R. Novelli, I. Mitchell, D. L. Stoker, D. M. Turnbull, J. A. Jankowski, N. A. Wright, Mechanisms of field cancerization in the human stomach: The expansion and spread of mutated gastric stem cells. Gastroenterology 134, 500-510 (2008).
104. S. S. Khurana, T. E. Riehl, B. D. Moore, M. Fassan, M. Rugge, J. Romero-Gallo, J. Noto, R. M. Peek Jr., W. F. Stenson, J. C. Mills, The hyaluronic acid receptor CD44 coordinates normal and metaplastic gastric epithelial progenitor cell proliferation. J. Biol. Chem. 288, 16085-16097 (2013).
105. J. R. Goldenring, G. S. Ray, R. J. Coffey, P. C. Meunier, P. J. Haley, T. B. Barnes, B. D. Car, Reversible drug-induced oxyntic atrophy in rats. Gastroenterology 118, 1080-1093 (2000).
106. A. Gupta, D. Wodziak, M. Tun, D. M. Bouley, A. W. Lowe, Loss of anterior gradient 2 (Agr2) expression results in hyperplasia and defective lineage maturation in the murine stomach. J. Biol. Chem. 288, 4321-4333 (2013).
107. M. Sashikawa Kimura, H. Mutoh, K. Sugano, SOX9 is expressed in normal stomach, intestinal metaplasia, and gastric carcinoma in humans. J. Gastroenterol. 46, 1292-1299 (2011).
108. C. P. Petersen, V. G. Weis, K. T. Nam, J. F. Sousa, B. Fingleton, J. R. Goldenring, Macrophages promote progression of spasmolytic polypeptide-expressing metaplasia after acute loss of parietal cells. Gastroenterology 146, 1727-1738.e8 (2014).
109. M. El-Zaatari, J. Y. Kao, A. Tessier, L. Bai, M. M. Hayes, C. Fontaine, K. A. Eaton, J. L. Merchant, Gli1 deletion prevents Helicobacter-induced gastric metaplasia and expansion of myeloid cell subsets. PLOS One 8, e58935 (2013).
110. K. Nozaki, V. Weis, T. C. Wang, A. Falus, J. R. Goldenring, Altered gastric chief cell lineage differentiation in histamine-deficient mice. Am. J. Physiol. Gastrointest. Liver Physiol. 296, G1211-G1220 (2009).
111. V. G. Weis, C. P. Petersen, J. C. Mills, P. L. Tuma, R. H. Whitehead, J. R. Goldenring, Establishment of novel in vitro mouse chief cell and SPEM cultures identifies MAL2 as a marker of metaplasia in the stomach. Am. J. Physiol. Gastrointest. Liver Physiol. 307, G777-G792 (2014).
112. T. Sato, R. G. Vries, H. J. Snippert, M. van de Wetering, N. Barker, D. E. Stange, J. H. van Es, A. Abo, P. Kujala, P. J. Peters, H. Clevers, Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459, 262-265 (2009).
113. T. H. Kim, F. Li, I. Ferreiro-Neira, L. L. Ho, A. Luyten, K. Nalapareddy, H. Long, M. Verzi, R. A. Shivdasani, Broadly permissive intestinal chromatin underlies lateral inhibition and cell plasticity. Nature 506, 511-515 (2014).
114. S. J. Buczacki, H. I. Zecchini, A. M. Nicholson, R. Russell, L. Vermeulen, R. Kemp, D. J. Winton, Intestinal label-retaining cells are secretory precursors expressing Lgr5. Nature 495, 65-69 (2013).
115. H. Tian, B. Biehs, S. Warming, K. G. Leong, L. Rangell, O. D. Klein, F. J. de Sauvage, A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable. Nature 478, 255-259 (2011).
116. L. G. Van der Flier, J. Sabates-Bellver, I. Oving, A. Haegebarth, M. De Palo, M. Anti, M. E. Van Gijn, S. Suijkerbuijk, M. Van de Wetering, G. Marra, H. Clevers, The intestinal Wnt/TCF signature. Gastroenterology 132, 628-632 (2007).
117. J. H. van Es, P. Jay, A. Gregorieff, M. E. van Gijn, S. Jonkheer, P. Hatzis, A. Thiele, M. van den Born, H. Begthel, T. Brabletz, M. M. Taketo, H. Clevers, Wnt signalling induces maturation of Paneth cells in intestinal crypts. Nat. Cell Biol. 7, 381-386 (2005).
118. N. Barker, J. H. van Es, J. Kuipers, P. Kujala, M. van den Born, M. Cozijnsen, A. Haegebarth, J. Korving, H. Begthel, P. J. Peters, H. Clevers, Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449, 1003-1007 (2007).
119. W. de Lau, N. Barker, T. Y. Low, B. K. Koo, V. S. Li, H. Teunissen, P. Kujala, A. Haegebarth, P. J. Peters, M. van de Wetering, D. E. Stange, J. E. van Es, D. Guardavaccaro, R. B. Schasfoort, Y. Mohri, K. Nishimori, S. Mohammed, A. J. Heck, H. Clevers, Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling. Nature 476, 293-297 (2011).
120. L. Vermeulen, H. J. Snippert, Stem cell dynamics in homeostasis and cancer of the intestine. Nat. Rev. Cancer 14, 468-480 (2014).
121. J. Munoz, D. E. Stange, A. G. Schepers, M. van de Wetering, B. K. Koo, S. Itzkovitz, R. Volckmann, K. S. Kung, J. Koster, S. Radulescu, K. Myant, R. Versteeg, O. J. Sansom, J. H. van Es, N. Barker, A. van Oudenaarden, S. Mohammed, A. J. Heck, H. Clevers, The Lgr5 intestinal stem cell signature: Robust expression of proposed quiescent '+4' cell markers. EMBO J. 31, 3079-3091 (2012).
122. V. W. Wong, D. E. Stange, M. E. Page, S. Buczacki, A. Wabik, S. Itami, M. van de Wetering, R. Poulsom, N. A. Wright, M. W. Trotter, F. M. Watt, D. J. Winton, H. Clevers, K. B. Jensen, Lrig1 controls intestinal stem-cell homeostasis by negative regulation of ErbB signalling. Nat. Cell Biol. 14, 401-408 (2012).
123. L. Van Landeghem, M. A. Santoro, A. E. Krebs, A. T. Mah, J. J. Dehmer, A. D. Gracz, B. P. Scull, K. McNaughton, S. T. Magness, P. K. Lund, Activation of two distinct Sox9-EGFP-expressing intestinal stem cell populations during crypt regeneration after irradiation. Am. J. Physiol. Gastrointest. Liver Physiol. 302, G1111-G1132 (2012).
124. S. Roth, P. Franken, A. Sacchetti, A. Kremer, K. Anderson, O. Sansom, R. Fodde, Paneth cells in intestinal homeostasis and tissue injury. PLOS One 7, e38965 (2012).
125. + secretory progenitor cells revert to stem cells upon crypt damage. Nat. Cell Biol. 14, 1099-1104 (2012).
126. S. E. Schonhoff, M. Giel-Moloney, A. B. Leiter, Neurogenin 3-expressing progenitor cells in the gastrointestinal tract differentiate into both endocrine and non-endocrine cell types. Dev. Biol. 270, 443-454 (2004).
127. C. B. Westphalen, S. Asfaha, Y. Hayakawa, Y. Takemoto, D. J. Lukin, A. H. Nuber, A. Brandtner, W. Setlik, H. Remotti, A. Muley, X. Chen, R. May, C. W. Houchen, J. G. Fox, M. D. Gershon, M. Quante, T. C. Wang, Long-lived intestinal tuft cells serve as colon cancer-initiating cells. J. Clin. Invest. 124, 1283-1295 (2014).
128. G. H. Ashton, J. P. Morton, K. Myant, T. J. Phesse, R. A. Ridgway, V. Marsh, J. A. Wilkins, D. Athineos, V. Muncan, R. Kemp, K. Neufeld, H. Clevers, V. Brunton, D. J. Winton, X. Wang, R. C. Sears, A. R. Clarke, M. C. Frame, O. J. Sansom, Focal adhesion kinase is required for intestinal regeneration and tumorigenesis downstream of Wnt/c-Myc signaling. Dev. Cell 19, 259-269 (2010).
129. + stem cells are indispensable for radiation-induced intestinal regeneration. Cell Stem Cell 14, 149-159 (2014).
130. M. Bienz, H. Clevers, Linking colorectal cancer to Wnt signaling. Cell 103, 311-320 (2000).
131. O. J. Sansom, K. R. Reed, A. J. Hayes, H. Ireland, H. Brinkmann, I. P. Newton, E. Batlle, P. Simon-Assmann, H. Clevers, I. S. Nathke, A. R. Clarke, D. J. Winton, Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration. Genes Dev. 18, 1385-1390 (2004).
132. P. Andreu, S. Colnot, C. Godard, S. Gad, P. Chafey, M. Niwa-Kawakita, P. Laurent-Puig, A. Kahn, S. Robine, C. Perret, B. Romagnolo, Crypt-restricted proliferation and commitment to the Paneth cell lineage following Apc loss in the mouse intestine. Development 132, 1443-1451 (2005).
133. + stem cell activity in mouse intestinal adenomas. Science 337, 730-735 (2012).
134. K. B. Myant, P. Cammareri, E. J. McGhee, R. A. Ridgway, D. J. Huels, J. B. Cordero, S. Schwitalla, G. Kalna, E. L. Ogg, D. Athineos, P. Timpson, M. Vidal, G. I. Murray, F. R. Greten, K. I. Anderson, O. J. Sansom, ROS production and NF-κB activation triggered by RAC1 facilitate WNT-driven intestinal stem cell proliferation and colorectal cancer initiation. Cell Stem Cell 12, 761-773 (2013).
135. C. Stringari, R. A. Edwards, K. T. Pate, M. L. Waterman, P. J. Donovan, E. Gratton, Metabolic trajectory of cellular differentiation in small intestine by Phasor Fluorescence Lifetime Microscopy of NADH. Sci. Rep. 2, 568 (2012).
136. K. T. Pate, C. Stringari, S. Sprowl-Tanio, K. Wang, T. TeSlaa, N. P. Hoverter, M. M. McQuade, C. Garner, M. A. Digman, M. A. Teitell, R. A. Edwards, E. Gratton, M. L. Waterman, Wnt signaling directs a metabolic program of glycolysis and angiogenesis in colon cancer. EMBO J. 33, 1454-1473 (2014).
137. Δ716 mice. Proc. Natl. Acad. Sci. U.S.A. 105, 13544-13549 (2008).
138. K. M. Hardiman, J. Liu, Y. Feng, J. K. Greenson, E. R. Fearon, Rapamycin inhibition of polyposis and progression to dysplasia in a mouse model. PLOS One 9, e96023 (2014).
139. W. J. Faller, T. J. Jackson, J. R. Knight, R. A. Ridgway, T. Jamieson, S. A. Karim, C. Jones, S. Radulescu, D. J. Huels, K. B. Myant, K. M. Dudek, H. A. Casey, A. Scopelliti, J. B. Cordero, M. Vidal, M. Pende, A. G. Ryazanov, N. Sonenberg, O. Meyuhas, M. N. Hall, M. Bushell, A. E. Willis, O. J. Sansom, mTORC1-mediated translational elongation limits intestinal tumour initiation and growth. Nature 517, 497-500 (2014).
140. Alert. Nature 510, 393-396 (2014).
141. N. Barker, R. A. Ridgway, J. H. van Es, M. van de Wetering, H. Begthel, M. van den Born, E. Danenberg, A. R. Clarke, O. J. Sansom, H. Clevers, Crypt stem cells as the cells-of-origin of intestinal cancer. Nature 457, 608-611 (2009).
142. S. L. Preston, W. M. Wong, A. O. Chan, R. Poulsom, R. Jeffery, R. A. Goodlad, N. Mandir, G. Elia, M. Novelli, W. F. Bodmer, I. P. Tomlinson, N. A. Wright, Bottom-up histogenesis of colorectal adenomas: Origin in the monocryptal adenoma and initial expansion by crypt fission. Cancer Res. 63, 3819-3825 (2003).
143. I. M. Shih, T. L. Wang, G. Traverso, K. Romans, S. R. Hamilton, S. Ben-Sasson, K. W. Kinzler, B. Vogelstein, Top-down morphogenesis of colorectal tumors. Proc. Natl. Acad. Sci. U.S.A. 98, 2640-2645 (2001).
144. S. Schwitalla, A. A. Fingerle, P. Cammareri, T. Nebelsiek, S. I. Goktuna, P. K. Ziegler, O. Canli, J. Heijmans, D. J. Huels, G. Moreaux, R. A. Rupec, M. Gerhard, R. Schmid, N. Barker, H. Clevers, R. Lang, J. Neumann, T. Kirchner, M. M. Taketo, G. R. van den Brink, O. J. Sansom, M. C. Arkan, F. R. Greten, Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties. Cell 152, 25-38 (2013).
145. W. J. Huh, E. Esen, J. H. Geahlen, A. J. Bredemeyer, A. H. Lee, G. Shi, S. F. Konieczny, L. H. Glimcher, J. C. Mills, XBP1 controls maturation of gastric zymogenic cells by induction of MIST1 and expansion of the rough endoplasmic reticulum. Gastroenterology 139, 2038-2049 (2010).
146. A. Kaser, A. H. Lee, A. Franke, J. N. Glickman, S. Zeissig, H. Tilg, E. E. Nieuwenhuis, D. E. Higgins, S. Schreiber, L. H. Glimcher, R. S. Blumberg, XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease. Cell 134, 743-756 (2008).
147. Cancer Genome Atlas Network, Comprehensive molecular characterization of human colon and rectal cancer. Nature 487, 330-337 (2012).
148. V600E-induced intestinal tumorigenesis reveals targets for therapeutic intervention. Cancer Cell 24, 15-29 (2013).
149. V. Marsh, D. J. Winton, G. T. Williams, N. Dubois, A. Trumpp, O. J. Sansom, A. R. Clarke, Epithelial Pten is dispensable for intestinal homeostasis but suppresses adenoma development and progression after Apc mutation. Nat. Genet. 40, 1436-1444 (2008).
150. P. Katajisto, K. Vaahtomeri, N. Ekman, E. Ventela, A. Ristimaki, N. Bardeesy, R. Feil, R. A. DePinho, T. P. Makela, LKB1 signaling in mesenchymal cells required for suppression of gastrointestinal polyposis. Nat. Genet. 40, 455-459 (2008).
151. S. Zac-Varghese, S. Trapp, P. Richards, S. Sayers, G. Sun, S. R. Bloom, F. Reimann, F. M. Gribble, G. A. Rutter, The Peutz-Jeghers kinase LKB1 suppresses polyp growth from intestinal cells of a proglucagon-expressing lineage in mice. Dis. Model. Mech. 7, 1275-1286 (2014).
152. A. P. Haramis, H. Begthel, M. van den Born, J. van Es, S. Jonkheer, G. J. Offerhaus, H. Clevers, De novo crypt formation and juvenile polyposis on BMP inhibition in mouse intestine. Science 303, 1684-1686 (2004).
153. H. Takabayashi, M. Shinohara, M. Mao, P. Phaosawasdi, M. El-Zaatari, M. Zhang, T. Ji, K. A. Eaton, D. Dang, J. Kao, A. Todisco, Anti-inflammatory activity of bone morphogenetic protein signaling pathways in stomachs of mice. Gastroenterology 147, 396-406.e7 (2014).
154. M. Shinohara, M. Mao, T. M. Keeley, M. El-Zaatari, H. J. Lee, K. A. Eaton, L. C. Samuelson, J. L. Merchant, J. R. Goldenring, A. Todisco, Bone morphogenetic protein signaling regulates gastric epithelial cell development and proliferation in mice. Gastroenterology 139, 2050-2060.e2 (2010).
155. H. Davis, S. Irshad, M. Bansal, H. Rafferty, T. Boitsova, C. Bardella, E. Jaeger, A. Lewis, L. Freeman-Mills, F. C. Giner, P. Rodenas-Cuadrado, S. Mallappa, S. Clark, H. Thomas, R. Jeffery, R. Poulsom, M. Rodriguez-Justo, M. Novelli, R. Chetty, A. Silver, O. J. Sansom, F. R. Greten, L. M. Wang, J. E. East, I. Tomlinson, S. J. Leedham, Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche. Nat. Med. 21, 62-70 (2014).
156. A. Lewis, L. Freeman-Mills, E. de la Calle-Mustienes, R. M. Giraldez-Perez, H. Davis, E. Jaeger, M. Becker, N. C. Hubner, L. N. Nguyen, J. Zeron-Medina, G. Bond, H. G. Stunnenberg, J. J. Carvajal, J. L. Gomez-Skarmeta, S. Leedham, I. Tomlinson, A polymorphic enhancer near GREM1 influences bowel cancer risk through differential CDX2 and TCF7L2 binding. Cell Rep. 8, 983-990 (2014).
157. Y. Feng, G. T. Bommer, J. Zhao, M. Green, E. Sands, Y. Zhai, K. Brown, A. Burberry, K. R. Cho, E. R. Fearon, Mutant Kras promotes hyperplasia and alters differentiation in the colon epithelium but does not expand the presumptive stem cell pool. Gastroenterology 141, 1003-1013.e10 (2011).
158. R. May, D. Qu, N. Weygant, P. Chandrakesan, N. Ali, S. A. Lightfoot, L. Li, S. M. Sureban, C. W. Houchen, Brief report: Dclk1 deletion in tuft cells results in impaired epithelial repair after radiation injury. Stem Cells 32, 822-827 (2014).
159. M. Giannakis, T. S. Stappenbeck, J. C. Mills, D. G. Leip, M. Lovett, S. W. Clifton, J. E. Ippolito, J. I. Glasscock, M. Arumugam, M. R. Brent, J. I. Gordon, Molecular properties of adult mouse gastric and intestinal epithelial progenitors in their niches. J. Biol. Chem. 281, 11292-11300 (2006).
160. H. Ireland, C. Houghton, L. Howard, D. J. Winton, Cellular inheritance of a Cre-activated reporter gene to determine Paneth cell longevity in the murine small intestine. Dev. Dyn. 233, 1332-1336 (2005).
161. H. Nitsche, S. Ramamoorthy, M. Sareban, N. Pausawasdi, A. Todisco, Functional role of bone morphogenetic protein-4 in isolated canine parietal cells. Am. J. Physiol. Gastrointest. Liver Physiol. 293, G607-G614 (2007).
162. C. L. Chaffer, R. A. Weinberg, How does multistep tumorigenesis really proceed? Cancer Discov. 5, 22-24 (2015).