title: The transcriptional landscape of αβ T cell differentiation.
abstract: 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.
authors: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
authors: Michael
authors: M
authors: Mingueneau
authors: Taras
authors: T
authors: Kreslavsky
authors: Daniel
authors: D
authors: Gray
authors: Tracy
authors: T
authors: Heng
authors: Richard
authors: R
authors: Cruse
authors: Jeffrey
authors: J
authors: Ericson
authors: Sean
authors: S
authors: Bendall
authors: Matthew H
authors: MH
authors: Spitzer
authors: Garry P
authors: GP
authors: Nolan
authors: Koichi
authors: K
authors: Kobayashi
authors: Harald
authors: H
authors: von Boehmer
authors: Diane
authors: D
authors: Mathis
authors: Christophe
authors: C
authors: Benoist
authors: Adam J
authors: AJ
authors: Best
authors: Jamie
authors: J
authors: Knell
authors: Ananda
authors: A
authors: Goldrath
authors: Vladimir
authors: V
authors: Joic
authors: Daphne
authors: D
authors: Koller
authors: Tal
authors: T
authors: Shay
authors: Aviv
authors: A
authors: Regev
authors: Nadia
authors: N
authors: Cohen
authors: Patrick
authors: P
authors: Brennan
authors: Michael
authors: M
authors: Brenner
authors: Francis
authors: F
authors: Kim
authors: Tata
authors: T
authors: Nageswara Rao
authors: Amy
authors: A
authors: Wagers
authors: Tracy
authors: T
authors: Heng
authors: Jeffrey
authors: J
authors: Ericson
authors: Katherine
authors: K
authors: Rothamel
authors: Adriana
authors: A
authors: Ortiz-Lopez
authors: Diane
authors: D
authors: Mathis
authors: Christophe
authors: C
authors: Benoist
authors: Natalie A
authors: NA
authors: Bezman
authors: Joseph C
authors: JC
authors: Sun
authors: Gundula
authors: G
authors: Min-Oo
authors: Charlie C
authors: CC
authors: Kim
authors: Lewis L
authors: LL
authors: Lanier
authors: Jennifer
authors: J
authors: Miller
authors: Brian
authors: B
authors: Brown
authors: Miriam
authors: M
authors: Merad
authors: Emmanuel L
authors: EL
authors: Gautier
authors: Claudia
authors: C
authors: Jakubzick
authors: Gwendalyn J
authors: GJ
authors: Randolph
authors: Paul
authors: P
authors: Monach
authors: David A
authors: DA
authors: Blair
authors: Michael L
authors: ML
authors: Dustin
authors: Susan A
authors: SA
authors: Shinton
authors: Richard R
authors: RR
authors: Hardy
authors: David
authors: D
authors: Laidlaw
authors: Jim
authors: J
authors: Collins
authors: Roi
authors: R
authors: Gazit
authors: Derrick J
authors: DJ
authors: Rossi
authors: Nidhi
authors: N
authors: Malhotra
authors: Katelyn
authors: K
authors: Sylvia
authors: Joonsoo
authors: J
authors: Kang
authors: Taras
authors: T
authors: Kreslavsky
authors: Anne
authors: A
authors: Fletcher
authors: Kutlu
authors: K
authors: Elpek
authors: Angelique
authors: A
authors: Bellemare-Pelletier
authors: Deepali
authors: D
authors: Malhotra
authors: Shannon
authors: S
authors: Turley
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D016000:Cluster Analysis; D005434:Flow Cytometry; D006649:Histocompatibility Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D060168:Thymocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics / Q000276:immunology; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D006649:Histocompatibility Antigens; D037181:Lectins, C-Type; D016693:Receptors, Antigen, T-Cell, alpha-beta; D000099192:CD69 Antigens
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