title: Expression profile of a clonal insulin-expressing epithelial cell in the thymus.
abstract: BACKGROUND
  Type 1 diabetes is an autoimmune disease resulting from the destruction of pancreatic beta-cells. One of the main antigens targeted in this auto reactive response is insulin. It has been shown that insulin is expressed in small amounts in the thymus, and more specifically in the medullary thymic epithelial cells (mTECs), which also express a variety of other tissue-specific antigens. This thymic expression enables the maintenance of self-tolerance, and is essential in preventing auto-immune disease. Our laboratory has created a mouse mTEC clonal cell line specifically expressing insulin in order to better understand the regulatory mechanisms of this ectopic expression of insulin. In this study, we compared the insulin expressing cell line to an insulin non-expressing mTEC line by genome-wide expression profiling.
  
  
  RESULTS
  The most important difference was overexpression of CD34 in the insulin expressing clone, confirmed by Real-time Rt-PCR and flow cytometry. Cells in the thymus expressing higher levels of CD34 were found to contain higher levels of insulin and, to a lesser extent, Aire, a master regulator of self-antigen expression in the thymus. The cells expressing CD34 were not enriched in CD80, a known mTEC maturity marker.
  
  
  CONCLUSIONS
  CD34 may be a specific marker for functionality, with some specificity for insulin.
authors: Endocrine Genetics, Research Institute of the McGill University Health Center, Montreal, Quebec, Canada.
authors: Dina
authors: D
authors: Levi
authors: Constantin
authors: C
authors: Polychronakos
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002999:Clone Cells / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D005434:Flow Cytometry; D007328:Insulin / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D018952:Antigens, CD34; C514817:Ins1 protein, mouse; C561967:Ins2 protein, mouse; D007328:Insulin
keywords: Autoimmunity; IFN-γ; Insulin; Self-antigens; TNF-α; Thymus; mTEC
references: Diabetologia. 2009 Oct;52(10):2151-8
references: 19609502
references: Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15854-9
references: 18836079
references: Science. 1993 Oct 15;262(5132):436-8
references: 7692600
references: Nat Genet. 1997 Mar;15(3):289-92
references: 9054944
references: Stat Med. 1990 Jul;9(7):811-8
references: 2218183
references: J Exp Med. 2005 Jul 4;202(1):33-45
references: 15983066
references: Science. 2002 Nov 15;298(5597):1395-401
references: 12376594
references: Int J Biochem Cell Biol. 2011 Dec;43(12):1668-73
references: 21964212
references: Nat Genet. 1997 Dec;17(4):393-8
references: 9398839
references: Clin Genet. 1985 Jun;27(6):535-42
references: 4017274
references: Diabetes. 2002 May;51(5):1383-90
references: 11978634
references: J Clin Invest. 2003 Mar;111(6):851-7
references: 12639991
references: Eur J Immunol. 2013 Jan;43(1):75-84
references: 23041971
references: Nature. 2003 Jun 19;423(6942):825-37
references: 12815422
references: J Immunol. 1992 Jan 1;148(1):267-71
references: 1370171
references: Diabetes. 2006 Sep;55(9):2595-601
references: 16936209
references: Proc Natl Acad Sci U S A. 2005 May 17;102(20):7233-8
references: 15883360
references: Curr Opin Gastroenterol. 2012 May;28(3):203-8
references: 22395569
references: Diabetes. 2004 Feb;53(2):354-9
references: 14747285
references: Immunity. 2005 Aug;23(2):227-39
references: 16111640
references: DNA Res. 1996 Oct 31;3(5):321-9, 341-54
references: 9039502
references: Nat Immunol. 2001 Nov;2(11):1032-9
references: 11600886
references: Cell. 2010 Jan 8;140(1):123-35
references: 20085707
references: EMBO J. 2009 Sep 16;28(18):2812-24
references: 19680229