Dynamic spatio-temporal contribution of single β5t+ cortical epithelial precursors to the thymus medulla

European Journal of Immunology

Volumn 46, Issue 4, 2016, Pages 846-856

  Mayer, Carlos E ^a   Žuklys, Saulius ^a   Zhanybekova, Saule ^a   Ohigashi, Izumi ^b   Teh, Hong Ying ^a   Sansom, Stephen N ^c   Shikama Dorn, Noriko ^a   Hafen, Katrin ^a   Macaulay, Iain C ^d   Deadman, Mary E ^f   Ponting, Chris P ^d,e   Takahama, Yousuke ^b   Holländer, Georg A ^a,f  

^a UNIVERSITY OF BASEL   (Switzerland)

^b UNIVERSITY OF TOKUSHIMA   (Japan)

^c UNIVERSITY OF OXFORD   (United Kingdom)

^d WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

^e UNIVERSITY OF OXFORD   (United Kingdom)

^f UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

Development; Epithelial cell; Medulla; Thymic progenitor cell; 5t

Indexed keywords

BETA5T PROTEIN; PROTEASOME; REVERSE TETRACYCLINE TRANSACTIVATOR; TRANSACTIVATOR PROTEIN; UNCLASSIFIED DRUG; DOXYCYCLINE; PROTEASOME SUBUNIT BETA5T, MOUSE;

ADULT; ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CELL DIFFERENTIATION; CELL LINEAGE; CELLULAR IMMUNITY; CONTROLLED STUDY; EPITHELIUM CELL; GENE EXPRESSION; IN VIVO STUDY; MOUSE; NONHUMAN; PRECURSOR; PRIORITY JOURNAL; PROTEIN EXPRESSION; THYMIC CORTEX; THYMIC EPITHELIAL CELL; THYMIC MEDULLA; ANIMAL; C57BL MOUSE; CELL PROLIFERATION; CYTOLOGY; EMBRYOLOGY; IMMUNOLOGY; KNOCKOUT MOUSE; METABOLISM; ORGANOGENESIS; PHYSIOLOGY; STEM CELL; T LYMPHOCYTE; THYMUS;

ANIMALS; CELL DIFFERENTIATION; CELL LINEAGE; CELL PROLIFERATION; DOXYCYCLINE; EPITHELIAL CELLS; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; ORGANOGENESIS; PROTEASOME ENDOPEPTIDASE COMPLEX; STEM CELLS; T-LYMPHOCYTES; THYMUS GLAND;

EID: 84962917590     PISSN: 00142980     EISSN: 15214141     Source Type: Journal    
DOI: 10.1002/eji.201545995     Document Type: Article

References (46)

1. Anderson, G. and Takahama, Y., Thymic epithelial cells: working class heroes for T cell development and repertoire selection. Trends Immunol. 2012. 33: 256-263.
2. Klein, L., Kyewski, B., Allen, P. M. and Hogquist, K. A., Positive and negative selection of the T cell repertoire: what thymocytes see (and don't see). Nat. Rev. Immunol. 2014. 14: 377-391.
3. Cowan, J. E., Parnell, S. M., Nakamura, K., Caamano, J. H., Lane, P. J. L., Jenkinson, E. J., Jenkinson, W. E. et al., The thymic medulla is required for Foxp3+ regulatory but not conventional CD4+ thymocyte development. J. Exp. Med. 2013. 210: 675-681.
4. Metzger, T. C. and Anderson, M. S., Control of central and peripheral tolerance by Aire. Immunol. Rev. 2011. 241: 89-103.
5. Daley, S. R., Hu, D. Y. and Goodnow, C. C., Helios marks strongly autoreactive CD4+ T cells in two major waves of thymic deletion distinguished by induction of PD-1 or NF-κB. J. Exp. Med. 2013. 210: 269-285.
6. Stritesky, G. L., Xing, Y., Erickson, J. R., Kalekar, L. A., Wang, X., Mueller, D. L., Jameson, S. C. et al., Murine thymic selection quantified using a unique method to capture deleted T cells. Proc. Natl. Acad. Sci. USA 2013. 110: 4679-4684.
7. Sansom, S. N., Shikama-Dorn, N., Zhanybekova, S., Nusspaumer, G., Macaulay, I. C., Deadman, M. E., Heger, A. et al., Population and single-cell genomics reveal the Aire dependency, relief from Polycomb silencing, and distribution of self-antigen expression in thymic epithelia. Genome Res. 2014. 24: 1918-1931.
8. Gill, J., Malin, M., Holländer, G. A. and Boyd, R., Generation of a complete thymic microenvironment by MTS24(+) thymic epithelial cells. Nat. Immunol. 2002. 3: 635-642.
9. Rossi, S. W., Jenkinson, W. E., Anderson, G. and Jenkinson, E. J., Clonal analysis reveals a common progenitor for thymic cortical and medullary epithelium. Nature 2006. 441: 988-991.
10. Rossi, S. W., Chidgey, A. P., Parnell, S. M., Jenkinson, W. E., Scott, H. S., Boyd, R. L., Jenkinson, E. J. et al., Redefining epithelial progenitor potential in the developing thymus. Eur. J. Immunol. 2007. 37: 2411-2418.
11. Bennett, A. R., Farley, A., Blair, N. F., Gordon, J., Sharp, L. and Blackburn, C. C., Identification and characterization of thymic epithelial progenitor cells. Immunity 2002. 16: 803-814.
12. Baik, S., Jenkinson, E. J., Lane, P. J. L., Anderson, G. and Jenkinson, W. E., Generation of both cortical and Aire(+) medullary thymic epithelial compartments from CD205(+) progenitors. Eur. J. Immunol. 2013. 43: 589-594.
13. Ribeiro, A. R., Rodrigues, P. M., Meireles, C., Di Santo, J. P. and Alves, N. L., Thymocyte selection regulates the homeostasis of IL-7-expressing thymic cortical epithelial cells in vivo. J. Immunol. 2013. 191: 1200-1209.
14. Alves, N. L., Takahama, Y., Ohigashi, I., Ribeiro, A. R., Baik, S., Anderson, G. and Jenkinson, W. E., Serial progression of cortical and medullary thymic epithelial microenvironments. Eur. J. Immunol. 2014. 44: 16-22.
15. Ohigashi, I., Zuklys, S., Sakata, M., Mayer, C. E., Zhanybekova, S., Murata, S., Tanaka, K. et al., Aire-expressing thymic medullary epithelial cells originate from β5t-expressing progenitor cells. Proc. Natl. Acad. Sci. USA 2013. 110: 9885-9890.
16. Bleul, C. C., Corbeaux, T., Reuter, A., Fisch, P., Mönting, J. S. and Boehm, T., Formation of a functional thymus initiated by a postnatal epithelial progenitor cell. Nature 2006. 441: 992-996.
17. Wong, K., Lister, N. L., Barsanti, M., Lim, J. M. C., Hammett, M. V., Khong, D. M., Siatskas, C. et al., Multilineage potential and self-renewal define an epithelial progenitor cell population in the adult thymus. Cell Rep. 2014. 8: 1198-1209.
18. Ucar, A., Ucar, O., Klug, P., Matt, S., Brunk, F., Hofmann, T. G. and Kyewski, B., Adult thymus contains FoxN1(-) epithelial stem cells that are bipotent for medullary and cortical thymic epithelial lineages. Immunity 2014. 41: 257-269.
19. Rodewald, H. R., Paul, S., Haller, C., Bluethmann, H. and Blum, C., Thymus medulla consisting of epithelial islets each derived from a single progenitor. Nature 2001. 414: 763-768.
20. Hamazaki, Y., Fujita, H., Kobayashi, T., Choi, Y., Scott, H. S., Matsumoto, M. and Minato, N., Medullary thymic epithelial cells expressing Aire represent a unique lineage derived from cells expressing claudin. Nat. Immunol. 2007. 8: 304-311.
21. Shakib, S., Desanti, G. E., Jenkinson, W. E., Parnell, S. M., Jenkinson, E. J. and Anderson, G., Checkpoints in the development of thymic cortical epithelial cells. J. Immunol. 2009. 182: 130-137.
22. Sekai, M., Hamazaki, Y. and Minato, N., Medullary thymic epithelial stem cells maintain a functional thymus to ensure lifelong central T cell tolerance. Immunity 2014. 41: 753-761.
23. Van Keymeulen, A., Rocha, A. S., Ousset, M., Beck, B., Bouvencourt, G., Rock, J., Sharma, N. et al., Distinct stem cells contribute to mammary gland development and maintenance. Nature 2011. 479: 189-193.
24. Schönig, K., Schwenk, F., Rajewsky, K. and Bujard, H., Stringent doxycycline dependent control of CRE recombinase in vivo. Nucleic Acids Res. 2002. 30: e134.
25. Madisen, L., Zwingman, T. A., Sunkin, S. M., Oh, S. W., Zariwala, H. A., Gu, H., Ng, L. L. et al., A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat. Neurosci. 2010. 13: 133-140.
26. Schaub, J. R., Malato, Y., Gormond, C. and Willenbring, H., Evidence against a stem cell origin of new hepatocytes in a common mouse model of chronic liver injury. Cell Rep. 2014. 8: 933-939.
27. Yanger, K., Knigin, D., Zong, Y., Maggs, L., Gu, G., Akiyama, H., Pikarsky, E. et al., Adult hepatocytes are generated by self-duplication rather than stem cell differentiation. Cell Stem Cell 2014. 15: 340-349
28. Dor, Y., Brown, J., Martinez, O. I. and Melton, D. A., Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature 2004. 429: 41-46.
29. Nishikawa, Y., Nishijima, H., Matsumoto, M., Morimoto, J., Hirota, F., Takahashi, S., Luche, H. et al., Temporal lineage tracing of Aire-expressing cells reveals a requirement for Aire in their maturation program. J. Immunol. 2014. 192: 2585-2592.
30. Dumont-Lagacé, M., Brochu, S., St-Pierre, C. and Perreault, C., Adult thymic epithelium contains nonsenescent label-retaining cells. J. Immunol. 2014. 192: 2219-2226.
31. Gray, D. H. D., Seach, N., Ueno, T., Milton, M. K., Liston, A., Lew, A. M., Goodnow, C. C. et al., Developmental kinetics, turnover, and stimulatory capacity of thymic epithelial cells. Blood 2006. 108: 3777-3785.
32. Gray, D., Abramson, J., Benoist, C. and Mathis, D., Proliferative arrest and rapid turnover of thymic epithelial cells expressing Aire. J. Exp. Med. 2007. 204: 2521-2528.
33. Snippert, H. J., van der Flier, L. G., Sato, T., van Es, J. H., van den Born, M., Kroon-Veenboer, C., Barker, N. et al., Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells. Cell 2010. 143: 134-144.
34. Onder, L., Nindl, V., Scandella, E., Chai, Q., Cheng, H.-W., Caviezel-Firner, S., Novkovic, M. et al., Alternative NF-κB signaling regulates mTEC differentiation from podoplanin-expressing presursors in the cortico-medullary junction. Eur. J. Immunol. 2015. 45: 2218-2231.
35. Rodewald, H.-R., Thymus organogenesis. Annu. Rev. Immunol. 2008. 26: 355-388.
36. Depreter, M. G. L., Blair, N. F., Gaskell, T. L., Nowell, C. S., Davern, K., Pagliocca, A., Stenhouse, F. H. et al., Identification of Plet-1 as a specific marker of early thymic epithelial progenitor cells. PNAS 2007. 105: 961-966.
37. Ripen, A. M., Nitta, T., Murata, S., Tanaka, K. and Takahama, Y., Ontogeny of thymic cortical epithelial cells expressing the thymoproteasome subunit β5t. Eur. J. Immunol. 2011. 41: 1278-1287.
38. Muñoz, J. J., Cejalvo, T., Tobajas, E., Fanlo, L., Cortés, A. and Zapata, A. G., 3D immunofluorescence analysis of early thymic morphogenesis and medulla development. Histol. Histopathol. 2015. 30: 589-599.
39. Rossi, S. W., Kim, M.-Y., Leibbrandt, A., Parnell, S. M., Jenkinson, W. E., Glanville, S. H., McConnell, F. M. et al., RANK signals from CD4(+)3(-) inducer cells regulate development of Aire-expressing epithelial cells in the thymic medulla. J. Exp. Med. 2007. 204: 1267-1272.
40. Nishikawa, Y., Hirota, F., Yano, M., Kitajima, H., Miyazaki, J., Kawamoto, H., Mouri, Y. et al., Biphasic Aire expression in early embryos and in medullary thymic epithelial cells before end-stage terminal differentiation. J. Exp. Med. 2010. 207: 963-971.
41. Ribeiro, A. R., Meireles, C., Rodrigues, P. M. and Alves, N. L., Intermediate expression of CCRL1 reveals novel subpopulations of medullary thymic epithelial cells that emerge in the postnatal thymus. Eur. J. Immunol. 2014. 44: 2918-2924.
42. Hsu, Y.-C., Li, L. and Fuchs, E., Transit-amplifying cells orchestrate stem cell activity and tissue regeneration. Cell 2014. 157: 935-949.
43. Ohigashi, I., Zuklys, S., Sakata, M., Mayer, C. E., Hamazaki, Y., Minato, N., Hollander, G. A. et al., Adult thymic medullary epithelium is maintained and regenerated by lineage-restricted cells rather than bipotent progenitors. Cell Rep. 2015. 13: 1-12.
44. Kawamoto, S., Niwa, H., Tashiro, F., Sano, S., Kondoh, G., Takeda, J., Tabayashi, K. et al., A novel reporter mouse strain that expresses enhanced green fluorescent protein upon Cre-mediated recombination. FEBS Lett. 2000. 470: 263-268.
45. Perl, A.-K. T., Wert, S. E., Nagy, A., Lobe, C. G. and Whitsett, J. A., Early restriction of peripheral and proximal cell lineages during formation of the lung. Proc. Natl. Acad. Sci. USA 2002. 99: 10482-10487.
46. Ramakers, C., Ruijter, J. M., Deprez, R. H. L. and Moorman, A. F., Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) data. Neurosci. Lett. 2003. 339: 62-66.