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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Main Authors: 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, A, Knell, J, Goldrath, A, Joic, V, Koller, D, Shay, T, Regev, A, Cohen, N, Brennan, P, Brenner, M, Kim, F, Nageswara Rao, T
Format: Journal article
Language:English
Published: 2013
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author 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, A
Knell, J
Goldrath, A
Joic, V
Koller, D
Shay, T
Regev, A
Cohen, N
Brennan, P
Brenner, M
Kim, F
Nageswara Rao, T
author_facet 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, A
Knell, J
Goldrath, A
Joic, V
Koller, D
Shay, T
Regev, A
Cohen, N
Brennan, P
Brenner, M
Kim, F
Nageswara Rao, T
author_sort Mingueneau, M
collection OXFORD
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(+)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.
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spelling oxford-uuid:d46269c8-de5c-4e4c-8903-dc31d5c6d65c2022-03-27T08:18:09ZThe transcriptional landscape of αβ T cell differentiation.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d46269c8-de5c-4e4c-8903-dc31d5c6d65cEnglishSymplectic Elements at Oxford2013Mingueneau, MKreslavsky, TGray, DHeng, TCruse, REricson, JBendall, SSpitzer, MNolan, GKobayashi, Kvon Boehmer, HMathis, DBenoist, CBest, AKnell, JGoldrath, AJoic, VKoller, DShay, TRegev, ACohen, NBrennan, PBrenner, MKim, FNageswara Rao, TThe 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(+)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.
spellingShingle 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, A
Knell, J
Goldrath, A
Joic, V
Koller, D
Shay, T
Regev, A
Cohen, N
Brennan, P
Brenner, M
Kim, F
Nageswara Rao, T
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
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