A general survey of thymocyte differentiation by transcriptional analysis of knockout mouse models.
The thymus is the primary site of T cell lymphopoiesis. To undergo proper differentiation, developing T cells follow a well-ordered genetic program that strictly depends on the heterogeneous and highly specialized thymic microenvironment. In this study, we used microarray technology to extensively describe transcriptional events regulating alphabeta T cell fate. To get an integrated view of these processes, both whole thymi from genetically engineered mice together with purified thymocytes were analyzed. Using mice exhibiting various transcriptional perturbations and developmental blockades, we performed a transcriptional microdissection of the organ. Multiple signatures covering both cortical and medullary stroma as well as various thymocyte maturation intermediates were clearly defined. Beyond the definition of histological and functional signatures (proliferation, rearrangement), we provide the first evidence that such an approach may also highlight the complex cross-talk events that occur between maturing T cells and stroma. Our data constitute a useful integrated resource describing the main gene networks set up during thymocyte development and a first step toward a more systematic transcriptional analysis of genetically modified mice.
Puthier
Denis
D
Technologies Avancées pour le Génome et la Clinique/ERM 206, Parc Scientifique de Luminy, 13288 Marseille cedex 09, France.
Joly
Florence
F
Irla
Magali
M
Saade
Murielle
M
Victorero
Geneviève
G
Loriod
Béatrice
B
Nguyen
Catherine
C
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D004265:DNA Helicases; D020869:Gene Expression Profiling / Q000379:methods; D015329:Gene Rearrangement, T-Lymphocyte; D019673:Genes, T-Cell Receptor alpha / Q000235:genetics; D007941:Leukemia P388; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics* / Q000276:immunology*; D023421:Models, Animal; D005810:Multigene Family / Q000276:immunology; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
C497762:Notch1 protein, mouse; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D015375:Receptors, Interleukin-2; C497594:Relb protein, mouse; D014157:Transcription Factors; D051841:Transcription Factor RelB; C513194:Smarca4 protein, mouse; D004265:DNA Helicases