The transcriptional landscape of αβ T cell differentiation
The differentiation of αβT 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...
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2014
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| Online Access: | http://hdl.handle.net/1721.1/85636 https://orcid.org/0000-0001-8567-2049 |
| _version_ | 1811097164901777408 |
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| author | Regev, Aviv |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Regev, Aviv |
| author_sort | Regev, Aviv |
| collection | MIT |
| description | The differentiation of αβT 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[superscript +]CD8[superscript +] 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[superscript +] or CD8[superscript +] 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. |
| first_indexed | 2024-09-23T16:55:23Z |
| format | Article |
| id | mit-1721.1/85636 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:55:23Z |
| publishDate | 2014 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/856362022-09-29T22:26:06Z The transcriptional landscape of αβ T cell differentiation Regev, Aviv Massachusetts Institute of Technology. Department of Biology Regev, Aviv The differentiation of αβT 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[superscript +]CD8[superscript +] 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[superscript +] or CD8[superscript +] 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. National Institutes of Health (U.S.) (AI072073) 2014-03-14T17:29:39Z 2014-03-14T17:29:39Z 2013-05 2012-11 Article http://purl.org/eprint/type/JournalArticle 1529-2908 1529-2916 http://hdl.handle.net/1721.1/85636 Mingueneau, Michael, Taras Kreslavsky, Daniel Gray, Tracy Heng, Richard Cruse, Jeffrey Ericson, Sean Bendall, et al. “The transcriptional landscape of αβ T cell differentiation.” Nature Immunology 14, no. 6 (May 5, 2013): 619-632. https://orcid.org/0000-0001-8567-2049 en_US http://dx.doi.org/10.1038/ni.2590 Nature Immunology Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Nature Publishing Group PMC |
| spellingShingle | Regev, Aviv The transcriptional landscape of αβ T cell differentiation |
| title | The transcriptional landscape of αβ T cell differentiation |
| title_full | The transcriptional landscape of αβ T cell differentiation |
| title_fullStr | The transcriptional landscape of αβ T cell differentiation |
| title_full_unstemmed | The transcriptional landscape of αβ T cell differentiation |
| title_short | The transcriptional landscape of αβ T cell differentiation |
| title_sort | transcriptional landscape of αβ t cell differentiation |
| url | http://hdl.handle.net/1721.1/85636 https://orcid.org/0000-0001-8567-2049 |
| work_keys_str_mv | AT regevaviv thetranscriptionallandscapeofabtcelldifferentiation AT regevaviv transcriptionallandscapeofabtcelldifferentiation |