The transcriptional landscape of alphabeta T cell differentiation

Michael Mingueneau, Taras Kreslavsky, Daniel Gray, Tracy Shu Ping Heng, Richard Cruse, Jeffrey Ericson, Sean Bendall, Matthew Wesley Spitzer, Garry Nolan, Koichi Kobayashi, Harald von Boehmer, Diane Mathis, Christophe Benoist, The Immunological Genome Consortium

Research output: Contribution to journalArticleResearchpeer-review

225 Citations (Scopus)


The differentiation of alphabetaT 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.
Original languageEnglish
Pages (from-to)619 - 632
Number of pages14
JournalNature Immunology
Issue number6
Publication statusPublished - 2013

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