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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

Alternative splicing of the gene encoding CD45 (Ptprc). (A) The first exons of the two Ptprc isoforms (Ptprc-201, Ptprc-202) annotated in the ENSEMBL GRCm38v70 mouse genome. Exons 4–6 (highlighted by grey box) are skipped in Ptprc-202 leading to a shorter transcript that is preferentially expressed following T cell activation. (B) Relative expression of Ptprc splice isoforms in the CD4+ subtypes was estimated using the mixture-of-isoforms (MISO) model to calculate percent spliced in (PSI) values for each isoform in each subtype.
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Fig10: Alternative splicing of the gene encoding CD45 (Ptprc). (A) The first exons of the two Ptprc isoforms (Ptprc-201, Ptprc-202) annotated in the ENSEMBL GRCm38v70 mouse genome. Exons 4–6 (highlighted by grey box) are skipped in Ptprc-202 leading to a shorter transcript that is preferentially expressed following T cell activation. (B) Relative expression of Ptprc splice isoforms in the CD4+ subtypes was estimated using the mixture-of-isoforms (MISO) model to calculate percent spliced in (PSI) values for each isoform in each subtype.

Mentions: Alternative splicing plays an important role in the regulation of eukaryotic gene regulation. To demonstrate the use of our data beyond gene-level differential expression we estimated isoform expression profiles in the subtypes using the mixture-of-isoforms (MISO) model [49]. We observed the previously reported change in major isoform for CD45 (Ptprc) [50] (Figure 10) and explored other aspects of alternative splicing during CD4+ T cell differentiation.Figure 10


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)

Alternative splicing of the gene encoding CD45 (Ptprc). (A) The first exons of the two Ptprc isoforms (Ptprc-201, Ptprc-202) annotated in the ENSEMBL GRCm38v70 mouse genome. Exons 4–6 (highlighted by grey box) are skipped in Ptprc-202 leading to a shorter transcript that is preferentially expressed following T cell activation. (B) Relative expression of Ptprc splice isoforms in the CD4+ subtypes was estimated using the mixture-of-isoforms (MISO) model to calculate percent spliced in (PSI) values for each isoform in each subtype.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig10: Alternative splicing of the gene encoding CD45 (Ptprc). (A) The first exons of the two Ptprc isoforms (Ptprc-201, Ptprc-202) annotated in the ENSEMBL GRCm38v70 mouse genome. Exons 4–6 (highlighted by grey box) are skipped in Ptprc-202 leading to a shorter transcript that is preferentially expressed following T cell activation. (B) Relative expression of Ptprc splice isoforms in the CD4+ subtypes was estimated using the mixture-of-isoforms (MISO) model to calculate percent spliced in (PSI) values for each isoform in each subtype.
Mentions: Alternative splicing plays an important role in the regulation of eukaryotic gene regulation. To demonstrate the use of our data beyond gene-level differential expression we estimated isoform expression profiles in the subtypes using the mixture-of-isoforms (MISO) model [49]. We observed the previously reported change in major isoform for CD45 (Ptprc) [50] (Figure 10) and explored other aspects of alternative splicing during CD4+ T cell differentiation.Figure 10

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