Macrophage-derived extracellular vesicle-packaged WNTs rescue intestinal stem cells and enhance survival after radiation injury

Nature Communications

Volumn 7, Issue , 2016, Pages

  Saha, Subhrajit ^a,c,e   Aranda, Evelyn ^a   Hayakawa, Yoku ^b   Bhanja, Payel ^a,e   Atay, Safinur ^c   Brodin, N Patrik ^a   Li, Jiufeng ^a   Asfaha, Samuel ^b   Liu, Laibin ^a   Tailor, Yagnesh ^b   Zhang, Jinghang ^a   Godwin, Andrew K ^c   Tome, Wolfgang A ^a   Wang, Timothy C ^b   Guha, Chandan ^a   Pollard, Jeffrey W ^a,d  

^a ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^b Department of Medicine   (United States)

^c UNIVERSITY OF KANSAS SCHOOL OF MEDICINE   (United States)

^d UNIVERSITY OF EDINBURGH   (United Kingdom)

^e UNIVERSITY OF KANSAS MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACYLTRANSFERASE; BETA CATENIN; CD11 ANTIGEN; FLUORESCEIN ISOTHIOCYANATE DEXTRAN; MESSENGER RNA; NUCLEAR FACTOR Y; WNT1 PROTEIN; MEMBRANE PROTEIN; PORCN PROTEIN, MOUSE; WNT PROTEIN;

CELLS AND CELL COMPONENTS; GENETIC ANALYSIS; INHIBITION; INJURY; MORPHOLOGY; PROTEIN; RADIATION DAMAGE; RODENT; SURVIVAL;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL PROLIFERATION; CELL SURVIVAL; CONTROLLED STUDY; DNA ISOLATION; ENZYME LINKED IMMUNOSORBENT ASSAY; EXOSOME; FEMALE; GENE EXPRESSION; HISTOPATHOLOGY; INTESTINAL STEM CELL; MALE; MOUSE; NONHUMAN; PROTEIN DEPLETION; RADIATION INJURY; REAL TIME POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; TISSUE REPAIR; WNT SIGNALING PATHWAY; ANIMAL; CELL CULTURE; CYTOLOGY; GENETICS; INSTITUTE FOR CANCER RESEARCH MOUSE; INTESTINE MUCOSA; KAPLAN MEIER METHOD; KNOCKOUT MOUSE; MACROPHAGE; METABOLISM; STEM CELL; TRANSGENIC MOUSE; WNT SIGNALING;

MUS;

ACYLTRANSFERASES; ANIMALS; CELLS, CULTURED; EXTRACELLULAR VESICLES; FEMALE; INTESTINAL MUCOSA; KAPLAN-MEIER ESTIMATE; MACROPHAGES; MALE; MEMBRANE PROTEINS; MICE, INBRED ICR; MICE, KNOCKOUT; MICE, TRANSGENIC; RADIATION INJURIES; STEM CELLS; WNT PROTEINS; WNT SIGNALING PATHWAY;

EID: 84991702569     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms13096     Document Type: Article

References (62)

1. Kabiri, Z. et al. Stroma provides an intestinal stem cell niche in the absence of epithelial Wnts. Development 141, 2206-2215 (2014).
2. Saha, S. et al. Bone marrow stromal cell transplantation mitigates radiationinduced gastrointestinal syndrome in mice. PLoS ONE 6, e24072 (2011).
3. Smith, P. D. et al. Intestinal macrophages and response to microbial encroachment. Mucosal. Immunol. 4, 31-42 (2011).
4. Pull, S. L., Doherty, J. M., Mills, J. C., Gordon, J. I., Stappenbeck, T. S. Activated macrophages are an adaptive element of the colonic epithelial progenitor niche necessary for regenerative responses to injury. Proc. Natl Acad. Sci. USA 102, 99-104 (2005).
5. Saha, S. et al. TLR9 agonist protects mice from radiation-induced gastrointestinal syndrome. PLoS ONE 7, e29357 (2012).
6. Kuhnert, F. et al. Essential requirement for Wnt signaling in proliferation of adult small intestine and colon revealed by adenoviral expression of Dickkopf-1. Proc. Natl Acad. Sci. USA 101, 266-271 (2004).
7. Gregorieff, A. et al. Expression pattern of Wnt signaling components in the adult intestine. Gastroenterology 129, 626-638 (2005).
8. Clevers, H., Nusse, R. Wnt/beta-catenin signaling and disease. Cell 149, 1192-1205 (2012).
9. Bhanja, P. et al. Protective role of R-spondin1, an intestinal stem cell growth factor, against radiation-induced gastrointestinal syndrome in mice. PLoS ONE 4, e8014 (2009).
10. Kim, K. A. et al. Mitogenic influence of human R-spondin1 on the intestinal epithelium. Science 309, 1256-1259 (2005).
11. Zhao, J. et al. R-Spondin1 protects mice from chemotherapy or radiationinduced oral mucositis through the canonical Wnt/beta-catenin pathway. Proc. Natl Acad. Sci. USA 106, 2331-2336 (2009).
12. Zhao, J. et al. R-spondin1, a novel intestinotrophic mitogen, ameliorates experimental colitis in mice. Gastroenterology 132, 1331-1343 (2007).
13. Yan, K. S. et al. The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations. Proc. Natl Acad. Sci. USA 109, 466-471 (2012).
14. Cervantes, S., Yamaguchi, T. P., Hebrok, M. Wnt5a is essential for intestinal elongation in mice. Dev. Biol. 326, 285-294 (2009).
15. Davies, P. S., Dismuke, A. D., Powell, A. E., Carroll, K. H., Wong, M. H. Wnt-reporter expression pattern in the mouse intestine during homeostasis. BMC. Gastroenterol. 8, 57 (2008).
16. Zeve, D. et al. Wnt signaling activation in adipose progenitors promotes insulin-independent muscle glucose uptake. Cell. Metab. 15, 492-504 (2012).
17. Farin, H. F., Van Es, J. H., Clevers, H. Redundant sources of Wnt regulate intestinal stem cells and promote formation of Paneth cells. Gastroenterology 143, 1518-1529 e1517 (2012).
18. Najdi, R. et al. A uniform human Wnt expression library reveals a shared secretory pathway and unique signaling activities. Differentiation. 84, 203-213 (2012).
19. Proffitt, K. D., Virshup, D. M. Precise regulation of porcupine activity is required for physiological Wnt signaling. J. Biol. Chem. 287, 34167-34178 (2012).
20. Hofmann, K. A superfamily of membrane-bound O-acyltransferases with implications for wnt signaling. Trends. Biochem. Sci. 25, 111-112 (2000).
21. Biechele, S., Cox, B. J., Rossant, J. Porcupine homolog is required for canonical Wnt signaling and gastrulation in mouse embryos. Dev. Biol. 355, 275-285 (2011).
22. Kadowaki, T., Wilder, E., Klingensmith, J., Zachary, K., Perrimon, N. The segment polarity gene porcupine encodes a putative multitransmembrane protein involved in Wingless processing. Genes Dev. 10, 3116-3128 (1996).
23. Tanaka, K., Okabayashi, K., Asashima, M., Perrimon, N., Kadowaki, T. The evolutionarily conserved porcupine gene family is involved in the processing of the Wnt family. Eur. J. Biochem. 267, 4300-4311 (2000).
24. Coombs, G. S. et al. Modulation of Wnt/beta-catenin signaling and proliferation by a ferrous iron chelator with therapeutic efficacy in genetically engineered mouse models of cancer. Oncogene 31, 213-225 (2012).
25. Janda, C. Y., Waghray, D., Levin, A. M., Thomas, C., Garcia, K. C. Structural basis of Wnt recognition by Frizzled. Science 337, 59-64 (2012).
26. Stefater, 3rd J. A., Ren, S., Lang, R. A., Duffield, J. S. Metchnikoff's policemen: macrophages in development, homeostasis and regeneration. Trends. Mol. Med. 17, 743-752 (2011).
27. Wynn, T. A., Chawla, A., Pollard, J. W. Macrophage biology in development, homeostasis and disease. Nature 496, 445-455 (2013).
28. Lin, S. L. et al. Macrophage Wnt7b is critical for kidney repair and regeneration. Proc. Natl Acad. Sci. USA 107, 4194-4199 (2010).
29. Boulter, L. et al. Macrophage-derived Wnt opposes Notch signaling to specify hepatic progenitor cell fate in chronic liver disease. Nat. Med. 18, 572-579 (2012).
30. Deng, L. et al. A novel mouse model of inflammatory bowel disease links mammalian target of rapamycin-dependent hyperproliferation of colonic epithelium to inflammation-associated tumorigenesis. Am. J. Pathol. 176, 952-967 (2010).
31. Raposo, G., Stoorvogel, W. Extracellular vesicles: exosomes, microvesicles, and friends. J. Cell Biol. 200, 373-383 (2013).
32. Korinek, V. et al. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/-colon carcinoma. Science 275, 1784-1787 (1997).
33. Jackson, Jr. W. L., Gallagher, C., Myhand, R. C., Waselenko, J. K. Medical management of patients with multiple organ dysfunction arising from acute radiation syndrome. BJR Suppl. 27, 161-168 (2005).
34. Leibowitz, B. J. et al. Ionizing irradiation induces acute haematopoietic syndrome and gastrointestinal syndrome independently in mice. Nat. Commun. 5, 3494 (2014).
35. Dawson, P. A. et al. Reduced mucin sulfonation and impaired intestinal barrier function in the hyposulfataemic NaS1 null mouse. Gut 58, 910-919 (2009).
36. Zhang, L., Wrana, J. L. The emerging role of exosomes in Wnt secretion and transport. Curr. Opin. Genet. Dev. 27, 14-19 (2014).
37. Gross, J. C., Chaudhary, V., Bartscherer, K., Boutros, M. Active Wnt proteins are secreted on exosomes. Nat. Cell. Biol. 14, 1036-1045 (2012).
38. Takada, R. et al. Monounsaturated fatty acid modification of Wnt protein: its role in Wnt secretion. Dev. Cell. 11, 791-801 (2006).
39. Willert, K. et al. Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature 423, 448-452 (2003).
40. Mikels, A. J., Nusse, R. Purified Wnt5a protein activates or inhibits beta-catenin-TCF signaling depending on receptor context. PLoS Biol. 4, e115 (2006).
41. Tanaka, S., Terada, K., Nohno, T. Canonical Wnt signaling is involved in switching from cell proliferation to myogenic differentiation of mouse myoblast cells. J. Mol. Signal. 6, 12 (2011).
42. Barker, N., van de Wetering, M., Clevers, H. The intestinal stem cell. Genes Dev. 22, 1856-1864 (2008).
43. Buczacki, S. J. et al. Intestinal label-retaining cells are secretory precursors expressing Lgr5. Nature 495, 65-69 (2013).
44. Powell, D. W., Saada, J. I. Mesenchymal stem cells and prostaglandins may be critical for intestinal wound repair. Gastroenterology 143, 19-22 (2012).
45. Takeda, N. et al. Interconversion between intestinal stem cell populations in distinct niches. Science 334, 1420-1424 (2011).
46. van der Flier, L. G., Haegebarth, A., Stange, D. E., van de Wetering, M., Clevers, H. OLFM4 is a robust marker for stem cells in human intestine and marks a subset of colorectal cancer cells. Gastroenterology 137, 15-17 (2009).
47. Wong, V. W. et al. Lrig1 controls intestinal stem-cell homeostasis by negative regulation of ErbB signalling. Nat. Cell. Biol. 14, 401-408 (2012).
48. Hayakawa, Y. et al. CCK2R identifies and regulates gastric antral stem cell states and carcinogenesis. Gut 64, 544-553 (2014).
49. Metcalfe, C., Kljavin, N. M., Ybarra, R., de Sauvage, F. J. Lgr5\+ stem cells are indispensable for radiation-induced intestinal regeneration. Cell Stem Cell 14, 149-159 (2014).
50. San Roman, A. K., Jayewickreme, C. D., Murtaugh, L. C., Shivdasani, R. A. Wnt secretion from epithelial cells and subepithelial myofibroblasts is not required in the mouse intestinal stem cell niche in vivo. Stem Cell Rep. 2, 127-134 (2014).
51. Pollard, J. W. Tumour-educated macrophages promote tumour progression and metastasis. Nat. Rev. Cancer 4, 71-78 (2004).
52. Yeo, E. J. et al. Myeloid WNT7b mediates the angiogenic switch and metastasis in breast cancer. Cancer Res. 74, 2962-2973 (2014).
53. Stanley, E. R. Murine bone marrow-derived macrophages. Methods Mol. Biol. 5, 299-302 (1990).
54. Atay, S. et al. Oncogenic KIT-containing exosomes increase gastrointestinal stromal tumor cell invasion. Proc. Natl Acad. Sci. USA 111, 711-716 (2014).
55. Potten, C. S., Booth, C., Pritchard, D. M. The intestinal epithelial stem cell: the mucosal governor. Int. J. Exp. Pathol. 78, 219-243 (1997).
56. Barker, N., van den Born, M. Detection of beta-catenin localization by immunohistochemistry. Methods Mol. Biol. 468, 91-98 (2008).
57. Ferraris, R. P., Diamond, J. Crypt-villus site of glucose transporter induction by dietary carbohydrate in mouse intestine. Am. J. Physiol. 262, G1069-G1073 (1992).
58. Goodyear, A. W., Kumar, A., Dow, S., Ryan, E. P. Optimization of murine small intestine leukocyte isolation for global immune phenotype analysis. J. Immunol. Methods 405, 97-108 (2014).
59. Karhausen, J. et al. Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis. J. Clin. Invest. 114, 1098-1106 (2004).
60. Sato, T. et al. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature 469, 415-418 (2011).
61. Sato, T. et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459, 262-265 (2009).
62. Barker, N. et al. Lgr5(\+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro. Cell Stem Cell 6, 25-36 (2010).