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000127903 1001_ $$0P:(DE-HGF)0$$aMartins, Vera C$$b0$$eFirst author
000127903 245__ $$aCell competition is a tumour suppressor mechanism in the thymus.
000127903 260__ $$aLondon [u.a.]$$bNature Publ. Group$$c2014
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000127903 520__ $$aCell competition is an emerging principle underlying selection for cellular fitness during development and disease. Competition may be relevant for cancer, but an experimental link between defects in competition and tumorigenesis is elusive. In the thymus, T lymphocytes develop from precursors that are constantly replaced by bone-marrow-derived progenitors. Here we show that in mice this turnover is regulated by natural cell competition between young bone-marrow-derived and old thymus-resident progenitors that, although genetically identical, execute differential gene expression programs. Disruption of cell competition leads to progenitor self-renewal, upregulation of Hmga1, transformation, and T-cell acute lymphoblastic leukaemia (T-ALL) resembling the human disease in pathology, genomic lesions, leukaemia-associated transcripts, and activating mutations in Notch1. Hence, cell competition is a tumour suppressor mechanism in the thymus. Failure to select fit progenitors through cell competition may explain leukaemia in X-linked severe combined immune deficiency patients who showed thymus-autonomous T-cell development after therapy with gene-corrected autologous progenitors.
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000127903 650_7 $$2NLM Chemicals$$aHMGA Proteins
000127903 650_7 $$2NLM Chemicals$$aNotch1 protein, mouse
000127903 650_7 $$2NLM Chemicals$$aReceptor, Notch1
000127903 7001_ $$0P:(DE-He78)6695811f3270b3dbe3d06842e2ca55cd$$aBusch, Katrin$$b1$$udkfz
000127903 7001_ $$0P:(DE-He78)5482b9f7e4c4ff6a3a4d7c860a1bce61$$aJuraeva, Dilafruz$$b2$$udkfz
000127903 7001_ $$aBlum, Carmen$$b3
000127903 7001_ $$aLudwig, Carolin$$b4
000127903 7001_ $$aRasche, Volker$$b5
000127903 7001_ $$aLasitschka, Felix$$b6
000127903 7001_ $$0P:(DE-HGF)0$$aMastitsky, Sergey E$$b7
000127903 7001_ $$0P:(DE-He78)fc949170377b58098e46141d95c72661$$aBrors, Benedikt$$b8$$udkfz
000127903 7001_ $$0P:(DE-He78)743a4a82daab55306a2c88b9f6bf8c2f$$aHielscher, Thomas$$b9$$udkfz
000127903 7001_ $$0P:(DE-HGF)0$$aFehling, Hans Joerg$$b10
000127903 7001_ $$0P:(DE-He78)86fa3316b7be0d661065d02b3baec3d6$$aRodewald, Hans-Reimer$$b11$$eLast author$$udkfz
000127903 773__ $$0PERI:(DE-600)1413423-8$$a10.1038/nature13317$$gVol. 509, no. 7501, p. 465 - 470$$n7501$$p465 - 470$$tNature <London>$$v509$$x1476-4687$$y2014
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