The transcriptional landscape of alpha beta T cell differentiation
- Author(s)
- Mingueneau, M; Kreslavsky, T; Gray, D; Heng, T; Cruse, R; Ericson, J; Bendall, S; Spitzer, M; Nolan, G; Kobayashi, K; von Boehmer, H; Mathis, D; Benoist, C; Best, AJ; Knell, J; Goldrath, A; Jojic, V; Koller, D; Shay, T; Regev, A; Cohen, N; Brennan, P; Brenner, M; Kim, F; Rao, TN; Wagers, A; Rothamel, K; Ortiz-Lopez, A; Bezman, NA; Sun, JC; Min-Oo, G; Kim, CC; Lanier, LL; Miller, J; Brown, B; Merad, M; Gautier, EL; Jakubzick, C; Randolph, GJ; Monach, P; Blair, DA; Dustin, ML; Shinton, SA; Hardy, RR; Laidlaw, D; Collins, J; Gazit, R; Rossi, DJ; Malhotra, N; Sylvia, K; Kang, J; Fletcher, A; Elpek, K; Bellemare-Pelletier, A; Malhotra, D; Turley, S;
- Details
- Publication Year 2013-06,Volume 14,Issue #6,Page 619-632
- Journal Title
- NATURE IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- The differentiation of abT cells from thymic precursors is a complex process essential for adaptive immunity. Here we exploited the breadth of expression data sets from the Immunological Genome Project to analyze how the differentiation of thymic precursors gives rise to mature T cell transcriptomes. We found that early T cell commitment was driven by unexpectedly gradual changes. In contrast, transit through the CD4(+)CD8(+) stage involved a global shutdown of housekeeping genes that is rare among cells of the immune system and correlated tightly with expression of the transcription factor c-Myc. Selection driven by major histocompatibility complex (MHC) molecules promoted a large-scale transcriptional reactivation. We identified distinct signatures that marked cells destined for positive selection versus apoptotic deletion. Differences in the expression of unexpectedly few genes accompanied commitment to the CD4(+) or CD8(+) lineage, a similarity that carried through to peripheral T cells and their activation, demonstrated by mass cytometry phosphoproteomics. The transcripts newly identified as encoding candidate mediators of key transitions help define the 'known unknowns' of thymocyte differentiation.
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- SELECTION IN-VIVO; GENE-EXPRESSION ANALYSIS; NEGATIVE SELECTION; POSITIVE SELECTION; PRE-TCR; C-MYC; CLONAL DELETION; LYMPHOCYTE DEVELOPMENT; INDUCED PROLIFERATION; THYMOCYTE SELECTION
- Research Division(s)
- Molecular Genetics Of Cancer
- Link To PubMed Central Version
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660436/
- Publisher's Version
- https://doi.org/10.1038/ni.2590
- Terms of Use/Rights Notice
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Creation Date: 2013-06-01 12:00:00