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An atlas of mouse CD4(+) T cell transcriptomes.

Stubbington MJ, Mahata B, Svensson V, Deonarine A, Nissen JK, Betz AG, Teichmann SA - Biol. Direct (2015)

Bottom Line: During an immune response Th cells mature from a naive state into one of several effector subtypes that exhibit distinct functions.To facilitate its use by others, we have made the data available in an easily accessible online resource at www.th-express.org .This article was reviewed by Wayne Hancock, Christine Wells and Erik van Nimwegen.

View Article: PubMed Central - PubMed

Affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, UK. mstubb@ebi.ac.uk.

ABSTRACT

Background: CD4(+) T cells are key regulators of the adaptive immune system and can be divided into T helper (Th) cells and regulatory T (Treg) cells. During an immune response Th cells mature from a naive state into one of several effector subtypes that exhibit distinct functions. The transcriptional mechanisms that underlie the specific functional identity of CD4(+) T cells are not fully understood.

Results: To assist investigations into the transcriptional identity and regulatory processes of these cells we performed mRNA-sequencing on three murine T helper subtypes (Th1, Th2 and Th17) as well as on splenic Treg cells and induced Treg (iTreg) cells. Our integrated analysis of this dataset revealed the gene expression changes associated with these related but distinct cellular identities. Each cell subtype differentially expresses a wealth of 'subtype upregulated' genes, some of which are well known whilst others promise new insights into signalling processes and transcriptional regulation. We show that hundreds of genes are regulated purely by alternative splicing to extend our knowledge of the role of post-transcriptional regulation in cell differentiation.

Conclusions: This CD4(+) transcriptome atlas provides a valuable resource for the study of CD4(+) T cell populations. To facilitate its use by others, we have made the data available in an easily accessible online resource at www.th-express.org .

Reviewers: This article was reviewed by Wayne Hancock, Christine Wells and Erik van Nimwegen.

No MeSH data available.


Related in: MedlinePlus

Skap1transcript switiching. (A) Splice isoforms of Skap1 annotated in the GRCm38v70 genome. The ‘functional’ isoforms encode a protein with a PH domain annotated in Pfam; isoforms 001 and 009 also contain an SH3 domain. Exons contributing to the domains are indicated in green (PH) and red (SH3). The truncated isoforms lack both PH and SH3 domains. Non-coding isoforms do not encode a protein. (B) Expression levels of Skap1 in the CD4+ subtypes. (C) Relative expression of Skap1 functional, truncated and non-coding isoforms for each CD4+ subtype. PSI values were summed for all full-length, truncated or non-coding isoforms.
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Fig12: Skap1transcript switiching. (A) Splice isoforms of Skap1 annotated in the GRCm38v70 genome. The ‘functional’ isoforms encode a protein with a PH domain annotated in Pfam; isoforms 001 and 009 also contain an SH3 domain. Exons contributing to the domains are indicated in green (PH) and red (SH3). The truncated isoforms lack both PH and SH3 domains. Non-coding isoforms do not encode a protein. (B) Expression levels of Skap1 in the CD4+ subtypes. (C) Relative expression of Skap1 functional, truncated and non-coding isoforms for each CD4+ subtype. PSI values were summed for all full-length, truncated or non-coding isoforms.

Mentions: Isoform quantitation can also provide new insights into gene regulation: the gene encoding the signalling adaptor SKAP-55 (Skap1) is an example. SKAP-55 is crucial for integrin activation following T lymphocyte stimulation and contains an SH3 domain and a pleckstrin homology (PH) domain [52-54] required for membrane localisation and protection from degradation respectively [52,55,56]. Skap1 has ten different splice isoforms (Figure 12A) and, whilst Skap1 is expressed at high levels in all subtypes (Figure 12B), there are striking differences in its isoform expression. Naive cells predominantly express the shortest truncated form lacking both SH3 and PH domains whilst in all differentiated subtypes the major Skap1 isoform encodes full-length protein (Figure 12C).Figure 12


An atlas of mouse CD4(+) T cell transcriptomes.

Stubbington MJ, Mahata B, Svensson V, Deonarine A, Nissen JK, Betz AG, Teichmann SA - Biol. Direct (2015)

Skap1transcript switiching. (A) Splice isoforms of Skap1 annotated in the GRCm38v70 genome. The ‘functional’ isoforms encode a protein with a PH domain annotated in Pfam; isoforms 001 and 009 also contain an SH3 domain. Exons contributing to the domains are indicated in green (PH) and red (SH3). The truncated isoforms lack both PH and SH3 domains. Non-coding isoforms do not encode a protein. (B) Expression levels of Skap1 in the CD4+ subtypes. (C) Relative expression of Skap1 functional, truncated and non-coding isoforms for each CD4+ subtype. PSI values were summed for all full-length, truncated or non-coding isoforms.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4384382&req=5

Fig12: Skap1transcript switiching. (A) Splice isoforms of Skap1 annotated in the GRCm38v70 genome. The ‘functional’ isoforms encode a protein with a PH domain annotated in Pfam; isoforms 001 and 009 also contain an SH3 domain. Exons contributing to the domains are indicated in green (PH) and red (SH3). The truncated isoforms lack both PH and SH3 domains. Non-coding isoforms do not encode a protein. (B) Expression levels of Skap1 in the CD4+ subtypes. (C) Relative expression of Skap1 functional, truncated and non-coding isoforms for each CD4+ subtype. PSI values were summed for all full-length, truncated or non-coding isoforms.
Mentions: Isoform quantitation can also provide new insights into gene regulation: the gene encoding the signalling adaptor SKAP-55 (Skap1) is an example. SKAP-55 is crucial for integrin activation following T lymphocyte stimulation and contains an SH3 domain and a pleckstrin homology (PH) domain [52-54] required for membrane localisation and protection from degradation respectively [52,55,56]. Skap1 has ten different splice isoforms (Figure 12A) and, whilst Skap1 is expressed at high levels in all subtypes (Figure 12B), there are striking differences in its isoform expression. Naive cells predominantly express the shortest truncated form lacking both SH3 and PH domains whilst in all differentiated subtypes the major Skap1 isoform encodes full-length protein (Figure 12C).Figure 12

Bottom Line: During an immune response Th cells mature from a naive state into one of several effector subtypes that exhibit distinct functions.To facilitate its use by others, we have made the data available in an easily accessible online resource at www.th-express.org .This article was reviewed by Wayne Hancock, Christine Wells and Erik van Nimwegen.

View Article: PubMed Central - PubMed

Affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, UK. mstubb@ebi.ac.uk.

ABSTRACT

Background: CD4(+) T cells are key regulators of the adaptive immune system and can be divided into T helper (Th) cells and regulatory T (Treg) cells. During an immune response Th cells mature from a naive state into one of several effector subtypes that exhibit distinct functions. The transcriptional mechanisms that underlie the specific functional identity of CD4(+) T cells are not fully understood.

Results: To assist investigations into the transcriptional identity and regulatory processes of these cells we performed mRNA-sequencing on three murine T helper subtypes (Th1, Th2 and Th17) as well as on splenic Treg cells and induced Treg (iTreg) cells. Our integrated analysis of this dataset revealed the gene expression changes associated with these related but distinct cellular identities. Each cell subtype differentially expresses a wealth of 'subtype upregulated' genes, some of which are well known whilst others promise new insights into signalling processes and transcriptional regulation. We show that hundreds of genes are regulated purely by alternative splicing to extend our knowledge of the role of post-transcriptional regulation in cell differentiation.

Conclusions: This CD4(+) transcriptome atlas provides a valuable resource for the study of CD4(+) T cell populations. To facilitate its use by others, we have made the data available in an easily accessible online resource at www.th-express.org .

Reviewers: This article was reviewed by Wayne Hancock, Christine Wells and Erik van Nimwegen.

No MeSH data available.


Related in: MedlinePlus