Mingueneau, MichaelKreslavsky, TarasGray, DanielHeng, TracyCruse, RichardEricson, JeffreyBendall, SeanSpitzer, MattNolan, GarryKobayashi, Koichivon Boehmer, HaraldMathis, DianeBenoist, Christophe2014-03-112013Mingueneau, M., T. Kreslavsky, D. Gray, T. Heng, R. Cruse, J. Ericson, S. Bendall, et al. 2013. “The transcriptional landscape of αβ T cell differentiation.” Nature immunology 14 (6): 10.1038/ni.2590. doi:10.1038/ni.2590. http://dx.doi.org/10.1038/ni.2590.1529-2908http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879434αβT cell differentiation from thymic precursors is a complex process, explored here with the breadth of ImmGen expression datasets, analyzing how differentiation of thymic precursors gives rise to transcriptomes. After surprisingly gradual changes though early T commitment, transit through the CD4+CD8+ stage involves a shutdown or rare breadth, and correlating tightly with MYC. MHC-driven selection promotes a large-scale transcriptional reactivation. We identify distinct signatures that mark cells destined for positive selection versus apoptotic deletion. Differential expression of surprisingly few genes accompany CD4 or CD8 commitment, a similarity that carries through to peripheral T cells and their activation, revealed by mass cytometry phosphoproteomics. The novel transcripts identified as candidate mediators of key transitions help define the “known unknown” of thymocyte differentiation.en-USJournal Article2014-03-1110.1038/ni.2590