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Expression data from CD4 single positive thymocyte subsets from C57BL/6 mice of 6-8 wks of age

ABSTRACT: After positive selection in the thymus, the newly generated single positive (SP) thymocytes are phenotypically and functionally immature and undergo apoptosis upon antigen stimulation. In the thymic medullary microenvironment, SP cells progressively acquire immunocompetence. Negative selection to remove autoreactive T cells also occur at this stage. We have defined four subsets of CD4 SP, namely, SP1, SP2, SP3, and SP4 that follow a functional maturation program and a sequential emergence during mouse ontogeny. We used microarray to detail the global programm of gene expression during the maturation of murine CD4 single positive thymocytes

ORGANISM(S): Mus musculus

PROVIDER: GSE30083 | GEO | 2012/02/13

SECONDARY ACCESSION(S): PRJNA143871

REPOSITORIES: GEO

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Expression data from CD4 single positive thymocyte subsets from C57BL/6 mice of 6-8 wks of age

Project description:After positive selection in the thymus, the newly generated single positive (SP) thymocytes are phenotypically and functionally immature and undergo apoptosis upon antigen stimulation. In the thymic medullary microenvironment, SP cells progressively acquire immunocompetence. Negative selection to remove autoreactive T cells also occur at this stage. We have defined four subsets of CD4 SP, namely, SP1, SP2, SP3, and SP4 that follow a functional maturation program and a sequential emergence during mouse ontogeny. We used microarray to detail the global programm of gene expression during the maturation of murine CD4 single positive thymocytes Four subsets of CD4+CD8-CD25-NK1.1- thymocytes from C57BL/6 mice of 6-8 wks of age were purified for RNA extraction and hybridization on Affymetrix microarrays, namely, SP1 (Qa-2-6C10+CD69+), SP2 (Qa-2-6C10-CD69+), SP3 (Qa-2-6C10-CD69-), SP4 (Qa-2+6C10-CD69-).

2012-02-13 | E-GEOD-30083 | biostudies-arrayexpress

The Gfi1-Foxo1 axis controls the fidelity of effector gene expression and developmental maturation of thymocytes

Project description:Double-positive (DP) thymocytes respond to intrathymic TCR signals by undergoing positive selection and lineage differentiation into single-positive (SP) mature cells. Concomitant with these wellcharacterized events is the acquisition of a mature T cell gene expression program characterized by the induction of effector molecules IL-7Ra, S1P1 and CCR7, but the underlying mechanism remains elusive. We report here that transcription repressor Gfi1 orchestrates the fidelity of DP gene expression program and developmental maturation into SP cells. Loss of Gfi1 resulted in premature induction of effector genes and transcription factors Foxo1 and Klf2 in DP thymocytes, and accumulation of post-selection intermediate populations and accelerated transition into SP cells. Strikingly, partial loss of Foxo1 function, but not restored survival fitness, rectified the dysregulated gene expression and thymocyte maturation in Gfi1-deficient mice. Our results establish Gfi1-Foxo1 axis and the transcriptional circuitry that actively maintain DP identity and shape the proper generation of mature T cells

2016-12-19 | GSE89898 | GEO

Role of splicing factor SRSF1 during the late stages of T cell maturation in the thymus

Project description:In thymus, the post-selection single positive thymocytes undergo further intrathymic maturation including down-regulation of CD69 and CD24, up-regulation of Qa-2, through which single positive thymocytes became equipped with emigration competency, then emigrate to periphery. Here we find that RNA binding protein Srsf1 is essential for the final maturation and survival of thymocytes.

2021-04-21 | GSE141349 | GEO

The pioneer transcription factors Foxa1 and Foxa2 regulate alternative RNA splicing during positive selection in the thymus

Project description:Here we show that the pioneer transcription factors Foxa1 and Foxa2 are required to regulate RNA splicing during positive selection at the transition from CD4+CD8+ double positive (DP) to single positive (SP thymocyte). Conditional deletion of both Foxa1 and Foxa2 from DP thymocytes led to a partial arrest at the transition from DP to SP, with a reduction in the number of cells undergoing positive selection, and reduced the number and maturation of both CD4SP and CD8SP populations, with a reduction in peripheral naïve CD4+ T-cells. Foxa1 and Foxa2 were required for physiological levels of expression of several genes which encoding splicing factors (Mbnl1, Sf3b1, Hnrnpa1) in cells undergoing positive selection. Within the positively selecting CD69+DP cells, alternative RNA splicing was dysregulated leading to more than 859 significantly differentially expressed exons compared to control, with many genes important for T cell development and for RNA splicing showing differentially used exons.

2021-07-13 | GSE169602 | GEO

Comparison of gene expression profiles by CD3+CD4+ thymocytes derived from fetal and adult hematopoietic stem cells

2010-12-17 | GSE25085 | GEO

Gene Expression Profile during human CD4+ T cell differentiation

Project description:Subpopulations of human fetal thymocyte and circulating naïve T cells were obtained through FACS sorting, including CD3-CD4+CD8- intrathymic T progenitor cells (ITTP), CD3intCD4+CD8+ "double positive" thymocytes (DP), CD3highCD4+CD8- "single positive" thymocytes (SP4), CD3+CD4+CD8-CD45RA+CD62L+ naïve T cells from cord blood (CB4+), and CD3+CD4+CD8-CD45RA+CD62L+ naïve T cells from adult blood (AB4+). Keywords = Microarray Keywords = gene expression Keywords = thymocytes Keywords = naïve CD4+ T cell Keywords = recent thymic emigrants Keywords: other

2004-07-01 | GSE1460 | GEO

Comparison of gene expression profiles by CD3+CD4+ thymocytes derived from fetal and adult hematopoietic stem cells

Project description:Human fetal and adult hematopoietic stem cells (HSC) were obtained from fetal liver, fetal bone marrow (BM), and adult BM. These were injected into human fetal thymic implants in SCID-hu Thy/Liv mice (4-6 separate mice per HSC donor) and allowed to mature into single positive CD4+ (SP4) thymocytes over the course of 7-8 weeks. SP4 thymocytes from injected stem cells were subsequently sort-purified from thymic implants and gene expression was performed. HSC from fetal (age 18-22 gestational weeks) and adult (age: 19-43 year old) HLA-A2+ donors were obtained from different tissues. After injection into human fetal thymic implants (SCID-hu Thy/Liv HLA-A2-) the cells were allowed to mature into thymocytes and sorted on the basis of HLA-A2+ expression and CD3+CD4+ (SP4) expression. 3 separate thymic implants were analyzed for each group.

2010-12-17 | E-GEOD-25085 | biostudies-arrayexpress

Transcription profiling of human fetal thymocytes and circulating naive T cells

Project description:Subpopulations of human fetal thymocyte and circulating naÃ¯ve T cells were obtained through FACS sorting, including CD3-CD4+CD8- intrathymic T progenitor cells (ITTP), CD3intCD4+CD8+ "double positive" thymocytes (DP), CD3highCD4+CD8- "single positive" thymocytes (SP4), CD3+CD4+CD8-CD45RA+CD62L+ naÃ¯ve T cells from cord blood (CB4+), and CD3+CD4+CD8-CD45RA+CD62L+ naÃ¯ve T cells from adult blood (AB4+).

2007-08-06 | E-GEOD-1460 | biostudies-arrayexpress

Gene expression profiling of thymocytes from conditional knock-out mice (FoxN1-Cre mediated KO of Gpr177)

Project description:Comparative gene expression profiling of thymocytes at the DP, CD4 SP and CD8 SP stage derived from FoxN1-Gpr177 mice (FoxN1-Cre mediated deletion of (Exon3 of) Gpr177/Wtls) or C57Bl/6N mice as comparison. Objective was to test the influence of TEC-secreted Wnt ligands on the transcriptome of thymocytes at the respective developmental stages. Total RNA extracted from FACS-sorted primary mouse thymocytes. CD4/8 double positive (DP) thymocytes, CD4 single positive (CD4 SP) thymocytes and CD8 single positive (CD8 SP) thymocytes were FACS-sorted from conditional knock-out mice (FoxN1-Gpr177) and C57Bl/6N mice as comparison.

2015-11-01 | E-GEOD-69766 | biostudies-arrayexpress

Late stages of T-cell maturation in the thymus involve NF-κB and tonic type I interferon signaling

Project description:Positive selection occurs in the thymic cortex, but critical maturation events occur later in the medulla. We defined the precise stage at which T cells acquire competence to proliferate and emigrate. Transcriptome analysis of late gene changes suggested roles for NF-κB and interferon signaling. Mice lacking the IKK kinase TAK1, showed normal positive selection, but a specific block in functional maturation. NF-κB signaling provided protection from TNF, and was required for proliferation and emigration. Alternatively, the interferon signature was independent of NF-κB, and IFNαR deficient thymocytes showed reduced STAT1 levels and phenotypic abnormality, but were competent to proliferate. Thus, both NF-κB and tonic IFN signals are involved in the final maturation of thymocytes into naïve T cells.

2016-04-03 | GSE74078 | GEO

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