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Characterization of Fetal Specific Transcriptional Programs in Thymic Epithelial Cells Identifies Myc as a Critical Determinant of Thymus Size

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE131368 | GEO | 2019/10/30

REPOSITORIES: GEO

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Characterization of Fetal Specific Transcriptional Programs in Thymic Epithelial Cells Identifies Myc as a Critical Determinant of Thymus Size [bulk RNA-Seq]

Project description:The thymus is the site of T cell development. Although much is known about the development and differentiation of the T lymphocyte compartment, less is known about the thymic epithelial cell (TEC) populations fostering their development. Here we use next generation sequencing approaches to identify transcriptional programs unique to TEC at specific stages of mouse life. This strategy identified Myc as a regulator of the fetal program, driving the rapid expansion in thymic size during fetal life.

2019-10-30 | GSE129192 | GEO

Characterization of Fetal Specific Transcriptional Programs in Thymic Epithelial Cells Identifies Myc as a Critical Determinant of Thymus Size [single cell RNA-Seq]

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Characterization of Fetal Specific Transcriptional Programs in Thymic Epithelial Cells Identifies Myc as a Critical Determinant of Thymus Size

Project description:Characterization of Fetal Specific Transcriptional Programs in Thymic Epithelial Cells Identifies Myc as a Critical Determinant of Thymus Size

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Characterization of Fetal Specific Transcriptional Programs in Thymic Epithelial Cells Identifies Myc as a Critical Determinant of Thymus Size [bulk RNA-Seq]

Project description:Characterization of Fetal Specific Transcriptional Programs in Thymic Epithelial Cells Identifies Myc as a Critical Determinant of Thymus Size [bulk RNA-Seq]

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Characterization of Fetal Specific Transcriptional Programs in Thymic Epithelial Cells Identifies Myc as a Critical Determinant of Thymus Size [single cell RNA-Seq]

Project description:Characterization of Fetal Specific Transcriptional Programs in Thymic Epithelial Cells Identifies Myc as a Critical Determinant of Thymus Size [single cell RNA-Seq]

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Myc controls a distinct transcriptional program in fetal thymic epithelial cells that determines thymus growth.

Project description:Interactions between thymic epithelial cells (TEC) and developing thymocytes are essential for T cell development, but molecular insights on TEC and thymus homeostasis are still lacking. Here we identify distinct transcriptional programs of TEC that account for their age-specific properties, including proliferation rates, engraftability and function. Further analyses identify Myc as a regulator of fetal thymus development to support the rapid increase of thymus size during fetal life. Enforced Myc expression in TEC induces the prolonged maintenance of a fetal-specific transcriptional program, which in turn extends the growth phase of the thymus and enhances thymic output; meanwhile, inducible expression of Myc in adult TEC similarly promotes thymic growth. Mechanistically, this Myc function is associated with enhanced ribosomal biogenesis in TEC. Our study thus identifies age-specific transcriptional programs in TEC, and establishes that Myc controls thymus size.

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Insights into Thymus Development and Viral Thymic Infections.

Project description:T-cell development in the thymus is a complex and highly regulated process, involving a wide variety of cells and molecules which orchestrate thymocyte maturation into either CD4+ or CD8+ single-positive (SP) T cells. Here, we briefly review the process regulating T-cell differentiation, which includes the latest advances in this field. In particular, we highlight how, starting from a pool of hematopoietic stem cells in the bone marrow, the sequential action of transcriptional factors and cytokines dictates the proliferation, restriction of lineage potential, T-cell antigen receptors (TCR) gene rearrangements, and selection events on the T-cell progenitors, ultimately leading to the generation of mature T cells. Moreover, this review discusses paradigmatic examples of viral infections affecting the thymus that, by inducing functional changes within this lymphoid gland, consequently influence the behavior of peripheral mature T-lymphocytes.

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Tbata modulates thymic stromal cell proliferation and thymus function.

Project description:Niche availability provided by stromal cells is critical to thymus function. Thymi with diminished function contain fewer stromal cells, whereas thymi with robust function contain proliferating stromal cell populations. Here, we show that the thymus, brain, and testes-associated gene (Tbata; also known as SPATIAL) regulates thymic epithelial cell (TEC) proliferation and thymus size. Tbata is expressed in thymic stromal cells and interacts with the enzyme Uba3, thereby inhibiting the Nedd8 pathway and cell proliferation. Thymi from aged Tbata-deficient mice are larger and contain more dividing TECs than wild-type littermate controls. In addition, thymic reconstitution after bone marrow transplantation occurred more rapidly in Rag2(-/-)Tbata(-/-) mice than in Rag2(-/-)Tbata(+/+) littermate controls. These findings suggest that Tbata modulates thymus function by regulating stromal cell proliferation via the Nedd8 pathway.

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Gene expression profiling in porcine fetal thymus.

Project description:To obtain an initial overview of gene diversity and expression pattern in porcine thymus, 11,712 ESTs (Expressed Sequence Tags) from 100-day-old porcine thymus (FTY) were sequenced and 7,071 cleaned ESTs were used for gene expression analysis. Clustered by the PHRAP program, 959 contigs and 3,074 singlets were obtained. Blast search showed that 806 contigs and 1,669 singlets (totally 5,442 ESTs) had homologues in GenBank and 1,629 ESTs were novel. According to the Gene Ontology classification, 36.99% ESTs were cataloged into the gene expression group, indicating that although the functional gene (18.78% in defense group) of thymus is expressed in a certain degree, the 100-day-old porcine thymus still exists in a developmental stage. Comparative analysis showed that the gene expression pattern of the 100-day-old porcine thymus is similar to that of the human infant thymus.

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