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http://dx.doi.org/10.14348/molcells.2015.0044

Expression Analyses Revealed Thymic Stromal Co-Transporter/Slc46A2 Is in Stem Cell Populations and Is a Putative Tumor Suppressor  

Kim, Ki Yeon (Department of Biological Sciences, Inha University)
Lee, Gwanghee (Department of Cell Biology and Physiology, Washington University School of Medicine)
Yoon, Minsang (Department of Biological Sciences, Inha University)
Cho, Eun Hye (Department of Biological Sciences, Inha University)
Park, Chan-Sik (Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center)
Kim, Moon Gyo (Department of Biological Sciences, Inha University)
Abstract
By combining conventional single cell analysis with flow cytometry and public database searches with bioinformatics tools, we extended the expression profiling of thymic stromal cotransporter (TSCOT), Slc46A2/Ly110, that was shown to be expressed in bipotent precursor and cortical thymic epithelial cells. Genome scale analysis verified TSCOT expression in thymic tissue- and cell type- specific fashion and is also expressed in some other epithelial tissues including skin and lung. Coexpression profiling with genes, Foxn1 and Hoxa3, revealed the role of TSCOT during the organogenesis. TSCOT expression was detected in all thymic epithelial cells (TECs), but not in the $CD31^+$endothelial cell lineage in fetal thymus. In addition, ABC transporter-dependent side population and Sca-$1^+$ fetal TEC populations both contain TSCOT-expressing cells, indicating TEC stem cells express TSCOT. TSCOT expression was identified as early as in differentiating embryonic stem cells. TSCOT expression is not under the control of Foxn1 since TSCOT is present in the thymic rudiment of nude mice. By searching variations in the expression levels, TSCOT is positively associated with Grhl3 and Irf6. Cytokines such as IL1b, IL22 and IL24 are the potential regulators of the TSCOT expression. Surprisingly, we found TSCOT expression in the lung is diminished in lung cancers, suggesting TSCOT may be involved in the suppression of lung tumor development. Based on these results, a model for TEC differentiation from the stem cells was proposed in context of multiple epithelial organ formation.
Keywords
Ly110; SLC46A2; stem cell; thymic epithelial cell; TSCOT; tumor suppressor;
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1 Sutherland, J.S., Goldberg, G.L., Hammett, M.V., Uldrich, A.P., Berzins, S.P., Heng, T.S., Blazar, B.R., Millar, J.L., Malin, M.A., Chidgey, A.P., et al. (2005). Activation of thymic regeneration in mice and humans following androgen blockade. J. Immunol. 175, 2741-2753.   DOI
2 Swann, J.B., and Boehm, T. (2007). Back to the beginning - the quest for thymic epithelial stem cells. Eur. J. Immunol. 37, 2364- 2366.   DOI   ScienceOn
3 Ucar, A., Ucar, O., Klug, P., Matt, S., Brunk, F., Hofmann, T.G., and Kyewski, B. (2014). Adult thymus Contains FoxN1- epithelial stem cells that are bipotent for medullary and cortical thymic epithelial lineages. Immunity 41, 257-269.   DOI   ScienceOn
4 Wallin, J., Eibel, H., Neubuser, A., Wilting, J., Koseki, H., and Balling, R. (1996). Pax1 is expressed during development of the thymus epithelium and is required for normal T-cell maturation. Development 122, 23-30.
5 Watson, A.P., Evans, R.L., and Egland, K.A. (2013). Multiple functions of sushi domain containing 2 (SUSD2) in breast tumorigenesis. Mol. Cancer Res. 11, 74-85.   DOI   ScienceOn
6 Wei, Q., and Condie, B.G. (2011). A focused in situ hybridization screen identifies candidate transcriptional regulators of thymic epithelial cell development and function. PLoS One 6, e26795.   DOI
7 Wong, K., Lister, N.L., Barsanti, M., Lim, J.M., Hammett, M.V., Khong, D.M., Siatskas, C., Gray, D.H., Boyd, R.L., and Chidgey, A.P. (2014). Multilineage potential and self-renewal define an epithelial progenitor cell population in the adult thymus. Cell Rep. 8, 1198-1209.   DOI   ScienceOn
8 Ahn, S., Lee, G., Yang, S.J., Lee, D., Lee, S., Shin, H.S., Kim, M.C., Lee, K.N., Palmer, D.C., Theoret, M.R., et al. (2008). TSCOT+ thymic epithelial cell-mediated sensitive CD4 tolerance by direct presentation. PLos Biol. 6, e191.   DOI   ScienceOn
9 Alves, N.L., Takahama, Y., Ohigashi, I., Ribeiro, A.R., Baik, S., Anderson, G., and Jenkinson, W.E. (2014). Serial progression of cortical and medullary thymic epithelial microenvironments. Eur. J. Immunol. 44, 16-22.   DOI   ScienceOn
10 Balciunaite, G., Keller, M.P., Balciunaite, E., Piali, L., Zuklys, S., Mathieu, Y.D., Gill, J., Boyd, R., Sussman, D.J., and Hollander, G.A. (2002). Wnt glycoproteins regulate the expression of FoxN1, the gene defective in nude mice. Nat. Immunol. 3, 1102-1108.   DOI   ScienceOn
11 Bellavia, D., Checquolo, S., Campese, A.F., Felli, M.P., Gulino, A., and Screpanti, I. (2008). Notch3: from subtle structural differences to functional diversity. Oncogene 27, 5092-5098.   DOI   ScienceOn
12 Bennett, A.R., Farley, A., Blair, N.F., Gordon, J., Sharp, L., and Blackburn, C.C. (2002). Identification and characterization of thymic epithelial progenitor cells. Immunity 16, 803-814.   DOI   ScienceOn
13 Berzins, S.P., Uldrich, A.P., Sutherland, J.S., and Gill, J. (2002). Thymic regeneration: teaching an old immune system new tricks. Trends Mol. Med. 8, 469-476.   DOI   ScienceOn
14 Blackburn, C.C., and Manley, N.R. (2004). Developing a new paradigm for thymus organogenesis. Nat. Rev. Immunol. 4, 278-289.   DOI   ScienceOn
15 Zhou, S., Schuetz, J.D., Bunting, K.D., Colapietro, A.M., Sampath, J., Morris, J.J., Lagutina, I., Grosveld, G.C., Osawa, M., Nakauchi, H., et al. (2001). The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat. Med. 7, 1028-1034.   DOI   ScienceOn
16 Yang, S.J., Ahn, S., Park, C.S., Choi, S., and Kim, M.G. (2005). Identifying subpopulations of thymic epithelial cells by flow cytometry using a new specific thymic epithelial marker, Ly110. J. Immunol. Methods 297, 265-270.   DOI   ScienceOn
17 Yu, Z., Bhandari, A., Mannik, J., Pham, T., Xu, X., and Andersen, B. (2008). Grainyhead-like factor Get1/Grhl3 regulates formation of the epidermal leading edge during eyelid closure. Dev. Biol. 319, 56-67.   DOI   ScienceOn
18 Zamisch, M., Moore-Scott, B., Su, D.M., Lucas, P.J., Manley, N., and Richie, E.R. (2005). Ontogeny and regulation of IL-7- expressing thymic epithelial cells. J. Immunol. 174, 60-67.   DOI
19 Blackburn, C.C., Manley, N.R., Palmer, D.B., Boyd, R.L., Anderson, G., and Ritter, M.A. (2002). One for all and all for one: thymic epithelial stem cells and regeneration. Trends Immunol. 23, 391-395.   DOI   ScienceOn
20 Blackburn, C.C., Augustine, C.L., Li, R., Harvey, R.P., Malin, M.A., Boyd, R.L., Miller, J.F., and Morahan, G. (1996). The nu gene acts cell-autonomously and is required for differentiation of thymic epithelial progenitors. Proc. Natl. Acad. Sci. USA 93, 5742-5746.   DOI
21 Bleul, C.C., and Boehm, T. (2005). BMP signaling is required for normal thymus development. J. Immunol. 175, 5213-5221.   DOI
22 Bleul, C.C., Corbeaux, T., Reuter, A., Fisch, P., Monting, J.S., and Boehm, T. (2006). Formation of a functional thymus initiated by a postnatal epithelial progenitor cell. Nature 441, 992-996.   DOI   ScienceOn
23 Boehm, T. (2008). Thymus development and function. Curr. Opin. Immunol. 20, 178-184.   DOI   ScienceOn
24 Bonfanti, P., Claudinot, S., Amici, A.W., Farley, A., Blackburn, C.C., and Barrandon, Y. (2010). Microenvironmental reprogramming of thymic epithelial cells to skin multipotent stem cells. Nature 466, 978-982.   DOI   ScienceOn
25 Botti, E., Spallone, G., Moretti, F., Marinari, B., Pinetti, V., Galanti, S., De Meo, P.D., De Nicola, F., Ganci, F., Castrignano, T., et al. (2011). Developmental factor IRF6 exhibits tumor suppressor activity in squamous cell carcinomas. Proc. Natl. Acad. Sci. USA 108, 13710-13715.   DOI   ScienceOn
26 Bredenkamp, N., Nowell, C.S., and Blackburn, C.C. (2014). Regeneration of the aged thymus by a single transcription factor. Development 141, 1627-1637.   DOI   ScienceOn
27 Cheng, L., Guo, J., Sun, L., Fu, J., Barnes, P.F., Metzger, D., Chambon, P., Oshima, R.G., Amagai, T., and Su, D.M. (2010). Postnatal tissue-specific disruption of transcription factor FoxN1 triggers acute thymic atrophy. J. Biol. Chem. 285, 5836-5847.   DOI   ScienceOn
28 Brems, H., Park, C., Maertens, O., Pemov, A., Messiaen, L., Upadhyaya, M., Claes, K., Beert, E., Peeters, K., Mautner, V. (2009). Glomus tumors in neurofibromatosis type 1: genetic, functional, and clinical evidence of a novel association. Cancer Res. 69, 7393-7401.   DOI   ScienceOn
29 Chen, C., Kim, M.G., Soo Lyu, M., Kozak, C.A., Schwartz, R.H., and Flomerfelt, F.A. (2000). Characterization of the mouse gene, human promoter and human cDNA of TSCOT reveals strong interspecies homology. Biochim. Biophys. Acta 1493, 159-169.   DOI   ScienceOn
30 Chen, L., Xiao, S., and Manley, N.R. (2009). Foxn1 is required to maintain the postnatal thymic microenvironment in a dosagesensitive manner. Blood 113, 567-574.   DOI   ScienceOn
31 Chinn, I.K., Blackburn, C.C., Manley, N.R., and Sempowski, G.D. (2012). Changes in primary lymphoid organs with aging. Semin. Immunol. 24 309-320.   DOI   ScienceOn
32 Chu, G., Qi, S., Yang, G., Dou, K., Du, J., and Lu, Z. (2012). Gastrointestinal tract specific gene GDDR inhibits the progression of gastric cancer in a TFF1 dependent manner. Mol. Cell. Biochem. 359, 369-374.   DOI   ScienceOn
33 Cimpean, A.M., Encica, S., Raica, M., and Ribatti, D. (2011). SOX2 gene expression in normal human thymus and thymoma. Clin. Exp. Med. 11, 251-254.   DOI   ScienceOn
34 Corbeaux, T., Hess, I., Swann, J.B., Kanzler, B., Haas-Assenbaum, A., and Boehm, T. (2010). Thymopoiesis in mice depends on a Foxn1-positive thymic epithelial cell lineage. Proc. Natl. Acad. Sci. USA 107, 16613-16618.   DOI   ScienceOn
35 Dudakov, J.A., Hanash, A.M., Jenq, R.R., Young, L.F., Ghosh, A., Singer, N.V., West, M.L., Smith, O.M., Holland, A.M., Tsai, J.J., et al. (2012). Interleukin-22 drives endogenous thymic regeneration in mice. Science 336, 91-95.   DOI
36 de la Garza, G., Schleiffarth, J.R., Dunnwald, M., Mankad, A., Weirather, J.L., Bonde, G., Butcher, S., Mansour, T.A., Kousa, Y.A., Fukazawa, C.F., et al. (2012). Interferon regulatory factor 6 promotes differentiation of the periderm by activating expression of grainyhead-Like 3. J. Invest. Dermatol. 133, 68-77.
37 Diop-Bove, N., Jain, M., Scaglia, F., and Goldman, I.D. (2013). A novel deletion mutation in the proton-coupled folate transporter (PCFT, SLC46A1) in a Nicaraguan child with hereditary folate malabsorption. Gene 527, 673-74.   DOI   ScienceOn
38 Dooley, J., Erickson, M., Roelink, H., and Farr, A.G. (2005). Nude thymic rudiment lacking functional foxn1 resembles respiratory epithelium. Dev. Dyn. 233, 1605-1612.   DOI   ScienceOn
39 Engelmark, M.T., Ivansson, E.L., Magnusson, J.J., Gustavsson, I.M., Beskow, A.H., Magnusson, P.K.E., and Gyllensten, U.B. (2006). Identification of susceptibility loci for cervical carcinoma by genome scan of affected sib-pairs. Hum. Mol. Genet. 15, 3351-3360.   DOI   ScienceOn
40 Engelmark, M.T., Ivansson, E.L., Magnusson, J.J., Gustavsson, I.M., Wyoni, P.I., Ingman, M., Magnusson, P.K., and Gyllensten, U.B. (2008). Polymorphisms in 9q32 and TSCOT are linked to cervical cancer in affected sib-pairs with high mean age at diagnosis. Hum. Genet. 123, 437-443.   DOI
41 Gill, J., Malin, M., Hollander, G.A., and Boyd, R. (2002). Generation of a complete thymic microenvironment by MTS24+ thymic epithelial cells. Nat. Immunol. 3, 635-642.
42 Gordon, J., Patel, S.R., Mishina, Y., and Manley, N.R. (2010). Evidence for an early role for BMP4 signaling in thymus and parathyroid morphogenesis. Dev. Biol. 339, 141-154.   DOI   ScienceOn
43 Gill, J., Malin, M., Sutherland, J., Gray, D., Hollander, G., and Boyd, R. (2003). Thymic generation and regeneration. Immunol. Rev. 195, 28-50.   DOI   ScienceOn
44 Golebiewska, A., Brons, N.H., Bjerkvig, R., and Niclou, S.P. (2011). Critical appraisal of the side population assay in stem cell and cancer stem cell research. Cell Stem Cell 8, 136-147.   DOI   ScienceOn
45 Gordon, J., and Manley, N.R. (2011). Mechanisms of thymus organogenesis and morphogenesis. Development 138, 3865- 3878.   DOI   ScienceOn
46 Graf, U., Casanova, E.A., and Cinelli, P. (2011). The role of the leukemia inhibitory factor (LIF) - pathway in derivation and maintenance of murine pluripotent stem cells. Genes 2, 280-297.   DOI
47 Hetzer-Egger, C., Schorpp, M., Haas-Assenbaum, A., Balling, R., Peters, H., and Boehm, T. (2002). Thymopoiesis requires Pax9 function in thymic epithelial cells. Eur. J. Immunol. 32, 1175- 1181.   DOI
48 Hirayama, T., Asano, Y., Iida, H., Watanabe, T., Nakamura, T., and Goitsuka, R. (2014). Meis1 is required for the maintenance of postnatal thymic epithelial cells. PLoS One 9, e89885.   DOI   ScienceOn
49 Hollander, G., Gill, J., Zuklys, S., Iwanami, N., Liu, C., and Takahama, Y. (2006). Cellular and molecular events during early thymus development. Immunol. Rev. 209, 28-46.   DOI   ScienceOn
50 Huang, J., and Muegge, K. (2001). Control of chromatin accessibility for V(D)J recombination by interleukin-7. J. Leukoc. Biol. 69, 907-911.
51 Kho, A.T., Bhattacharya, S., Tantisira, K.G., Carey, V.J., Gaedigk, R., Leeder, J.S., Kohane, I.S., Weiss, S.T., and Mariani, T.J. (2010). Transcriptomic analysis of human lung development. Am. J. Respir. Crit. Care Med. 181, 54-63.   DOI   ScienceOn
52 Imaoka, S., Yoneda, Y., Sugimoto, T., Hiroi, T., Yamamoto, K., Nakatani, T., and Funae, Y. (2000). CYP4B1 is a possible risk factor for bladder cancer in humans. Biochem. Biophys. Res. Commun. 277, 776-780.   DOI   ScienceOn
53 Jerome, L.A., and Papaioannou, V.E. (2001). DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1. Nat. Genet. 27, 286-291.   DOI   ScienceOn
54 Jiang, W., Swiggard, W.J., Heufler, C., Peng, M., Mirza, A., Steinman, R.M., and Nussenzweig, M.C. (1995). The receptor DEC- 205 expressed by dendritic cells and thymic epithelial cells is involved in antigen processing. Nature 375, 151-155.   DOI   ScienceOn
55 Kim, M.G., Chen, C., Flomerfelt, F.A., Germain, R.N., and Schwartz, R.H. (1998). A subtractive PCR-based cDNA library made from fetal thymic stromal cells. J. Immunol. Methods 213, 169-182.   DOI   ScienceOn
56 Kim, M.G., Flomerfelt, F.A., Lee, K.N., Chen, C., and Schwartz, R.H. (2000). A putative 12 transmembrane domain cotransporter expressed in thymic cortical epithelial cells. J. Immunol. 164, 3185-3192.   DOI
57 Kirchner, J., Forbush, K.A., and Bevan, M.J. (2001). Identification and Characterization of thymus LIM Protein: targeted disruption reduces thymus cellularity. Mol. Cell. Biol. 21, 8592-8604.   DOI   ScienceOn
58 Klug, D.B., Carter, C., Crouch, E., Roop, D., Conti, C.J., and Richie, E.R. (1998). Interdependence of cortical thymic epithelial cell differentiation and T-lineage commitment. Proc. Natl. Acad. Sci. USA 95, 11822-11827.   DOI
59 Lee, G., Kim, K.Y., Chang, C.H., and Kim, M.G. (2012). Thymic epithelial requirement for ${\gamma}{\delta}$ T cell development revealed in the cell ablation transgenic system with TSCOT promoter. Mol. Cells 34, 481-493.   DOI   ScienceOn
60 Klug, D.B., Carter, C., Gimenez-Conti, I.B., and Richie, E.R. (2002). Cutting edge: thymocyte-independent and thymocytedependent phases of epithelial patterning in the fetal thymus. J. Immunol. 169, 2842-2845.   DOI
61 Liang, H., Coles, A.H., Zhu, Z., Zayas, J., Jurecic, R., Kang, J., and Jones, S.N., (2007). Noncanonical Wnt signaling promotes apoptosis in thymocyte development. J. Exp. Med. 204, 3077-3084.   DOI   ScienceOn
62 Liu, J., Hadjokas, N., Mosley, B., Estrov, Z., Spence, M.J., and Vestal, R.E. (1998). Oncostatin M-specific receptor expression and function in regulating cell proliferation of normal and malignant mammary epithelial cells. Cytokine 10, 295-302.   DOI   ScienceOn
63 Liu, K., Lin, B., Zhao, M., Yang, X., Chen, M., Gao, A., Que, J., and Lan, X. (2013). The multiple roles for Sox2 in stem cell maintenance and tumorigenesis. Cell. Signal. 25, 1264-1271.   DOI   ScienceOn
64 Liu, G., Wang, L., Pang, T., Zhu, D., Xu, Y., Wang, H., Cong, X., and Liu, Y. (2014). Umbilical cord-derived mesenchymal stem cells regulate thymic epithelial cell development and function in Foxn1-/- mice. Cell. Mol. Immunol. 11, 275-284.   DOI
65 Lynch, H.E., Goldberg, G.L., Chidgey, A., Van den Brink, M.R., Boyd, R., and Sempowski, G.D. (2009). Thymic involution and immune reconstitution. Trends Immunol. 30, 366-373.   DOI   ScienceOn
66 Manley, N.R., Selleri, L., Brendolan, A., Gordon, J., and Cleary, M.L. (2004). Abnormalities of caudal pharyngeal pouch development in Pbx1 knockout mice mimic loss of Hox3 paralogs. Dev. Biol. 276, 301-312.   DOI   ScienceOn
67 Malik, S., Kakar, N., Hasnain, S., Ahmad, J., Wilcox, E.R., and Naz, S. (2010). Epidemiology of Van der Woude syndrome from mutational analyses in affected patients from Pakistan. Clin. Genet. 78, 247-256.   DOI   ScienceOn
68 Manley, N.R., and Capecchi, M.R. (1995). The role of Hoxa-3 in mouse thymus and thyroid development. Development 121, 1989-2003.
69 Manley, N.R., and Condie, B.G. (2010). Transcriptional regulation of thymus organogenesis and thymic epithelial cell differentiation. Prog. Mol. Biol. Transl. Sci. 92, 103-120.
70 Moore-Scott, B.A., and Manley, N.R. (2005). Differential expression of Sonic hedgehog along the anterior-posterior axis regulates patterning of pharyngeal pouch endoderm and pharyngeal endoderm- derived organs. Dev. Biol. 278, 323-335.   DOI   ScienceOn
71 Murata, S., Sasaki, K., Kishimoto, T., Niwa, S., Hayashi, H., Takahama, Y., and Tanaka, K. (2007). Regulation of CD8+ T cell development by thymus-specific proteasomes. Science 316, 1349-1353.   DOI   ScienceOn
72 Nehls, M., Kyewski, B., Messerle, M., Waldschutz, R., Schuddekopf, K., Smith, A.J., and Boehm, T. (1996). Two genetically separable steps in the differentiation of thymic epithelium. Science 272, 886-889.   DOI   ScienceOn
73 Nowell, C.S., Bredenkamp, N., Tetelin, S., Jin, X., Tischner, C., Vaidya, H., Sheridan, J.M., Stenhouse, F.H., Heussen, R., Smith, A.J., et al. (2011). Foxn1 regulates lineage progression in cortical and medullary thymic epithelial cells but Is dispensable for medullary sublineage divergence. PLoS Genet. 7, e1002348.   DOI
74 Potter, C.S., Pruett, N.D., Kern, M.J., Baybo, M.A., Godwin, A.R., Potter, K.A., Peterson, R.L., Sundberg, J.P., and Awgulewitsch, A. (2010). The nude mutant gene Foxn1 Is a HOXC13 regulatory target during hair follicle and nail differentiation. J. Invest. Dermatol. 131, 828-837.
75 Obermann, H., Wingbermuhle, A., Munz, S., and Kirchhoff, C. (2003). A putative 12-transmembrane domain cotransporter associated with apical membranes of the epididymal duct. J. Androl. 24, 542-556.   DOI
76 Park, D. (1997). Cloning, sequencing, and overexpression of SH2/SH3 adaptor protein Nck from mouse thymus. Mol. Cells 7, 231-236.
77 Park, C.S., Lee, G., Yang, S.J., Ahn, S., Kim, K.Y., Shin, H., and Kim, M.G. (2013). Differential lineage specification of thymic epithelial cells from bipotent precursors revealed by TSCOT promoter activities. Genes Immun. 14, 401-406.   DOI   ScienceOn
78 Richardson, R.J., Dixon, J., Malhotra, S., Hardman, M.J., Knowles, L., Boot-Handford, R.P., Shore, P., Whitmarsh, A., and Dixon, M.J. (2006). Irf6 is a key determinant of the keratinocyte proliferation- differentiation switch. Nat. Genet. 38, 1329-1334.   DOI   ScienceOn
79 Roberts, N.A., White, A.J., Jenkinson, W.E., Turchinovich, G., Nakamura, K., Withers, D.R., McConnell, F.M., Desanti, G.E., Benezech, C., Parnell, S.M., et al. (2012). Rank signaling links the development of invariant ${\gamma}{\delta}$ T cell progenitors and Aire(+) medullary epithelium. Immunity 36, 427-437.   DOI   ScienceOn
80 Rodewald, H.R. (2008). Thymus organogenesis. Annu. Rev. Immunol. 26, 355-388.   DOI   ScienceOn
81 Rodewald, H.R., Paul, S., Haller, C., Bluethmann, H., and Blum, C. (2001). Thymus medulla consisting of epithelial islets each derived from a single progenitor. Nature 414, 763-768.   DOI   ScienceOn
82 Shakib, S., Desanti, G.E., Jenkinson, W.E., Parnell, S.M., Jenkinson, E.J., and Anderson, G. (2009). Checkpoints in the development of thymic cortical epithelial cells. J. Immunol. 182, 130-137.   DOI
83 Rossi, S.W., Jenkinson, W.E., Anderson, G., and Jenkinson, E.J. (2006). Clonal analysis reveals a common progenitor for thymic cortical and medullary epithelium. Nature 441, 988-991.   DOI   ScienceOn
84 Sahin, U., Koslowski, M., Dhaene, K., Usener, D., Brandenburg, G., Seitz, G., Huber, C., and Tureci, O. (2008). Claudin-18 splice variant 2 is a Pan-cancer target suitable for therapeutic antibody development. Clin. Cancer Res. 14, 7624-7634.   DOI   ScienceOn
85 Saunders-Pullman, R., Barrett, M.J., Stanley, K.M., Luciano, M.S., Shanker, V., Severt, L., Hunt, A., Raymond, D., Ozelius, L.J., and Bressman, S.B. (2010). LRRK2G2019S mutations are associated with an increased cancer risk in Parkinson disease. Mov. Disord. 25, 2536-2541.   DOI   ScienceOn
86 Shen, M.M., and Leder, P. (1992). Leukemia inhibitory factor is expressed by the preimplantation uterus and selectively blocks primitive ectoderm formation in vitro. Proc. Natl. Acad. Sci. USA 89, 8240-8244.   DOI   ScienceOn
87 Su, D., Ellis, S., Napier, A., Lee, K., and Manley, N.R. (2001). Hoxa3 and Pax1 regulate epithelial cell death and proliferation during thymus and parathyroid organogenesis. Dev. Biol. 236, 316-329.   DOI   ScienceOn
88 Sun, L., Luo, H., Li, H., and Zhao, Y. (2013). Thymic epithelial cell development and differentiation: cellular and molecular regulation. Protein Cell 4, 342-355.   DOI   ScienceOn