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Thymic mimetic cells function beyond self-tolerance [Insm1]

ABSTRACT: To examine the Endocrine thymic epithelial cell transcriptome within the mTEC-III compartment we sorted this population from young Insm1 cKO mice and performed bulk RNAseq

ORGANISM(S): Mus musculus

PROVIDER: GSE236073 | GEO | 2023/08/28

REPOSITORIES: GEO

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Thymic mimetic cells function beyond self-tolerance [Spib]

Project description:To examine the Microfold thymic epithelial cell transcriptome within the mTEC-III compartment we sorted this population from young Spib KO mice and performed bulk RNAseq

2023-08-28 | GSE236074 | GEO

Insm1 regulates the expression of thymic tissue-restricted antigens and the immune tolerance [RNA-seq]

Project description:Insm1, encoding a zinc finger protein, is expressed specifically in neuroendocrine cells. Recent study showed the first evidence of Insm1 expression in medullary thymic epithelial cells (mTEC). Here we investigated the expression and function of Insm1 in mTEC. Mutation of Insm1 resulted in decreased proportion of mTEChi although normal development of other types of thymic cells. We detected altered expression of a subset of tissue-restricted antigens (TRAs) and mild decreased expression of Aire and Fezf2 in Insm1 mutant mTEC. We further showed that Insm1 recognizes a DNA sequence which is similar to the CCCTC-Binding factor (CTCF) binding motif. Mutation of Insm1 altered CTCF binding genome widely and thus the expression of genes. In nude mice transplanted with Insm1 mutant thymus, autoimmune responses were observed in multiple peripheral tissues. In thymus specific Insm1 mutant mice, we detected decreased induction of regulatory T (Treg) cells in the thymus, obvious lymphocytes infiltration and autoimmune antibody reaction in several peripheral tissues. In thymic epithelial cells specific Insm1 overexpression mice, we detected enlarged mTEC proportion and increased expression of mTEC specific genes. Thus, we suggest that Insm1 is a novel regulator of mTEC function and autoimmunity.

2024-01-01 | GSE193927 | GEO

Insm1 regulates the expression of thymic tissue-restricted antigens and the immune tolerance [CUT&Tag]

2024-01-01 | GSE193926 | GEO

Thymic mimetic cells function beyond self-tolerance [IgM and Ccr6]

Project description:To examine the microfold thymic epithelial cell transcriptome within the mTEC-III compartment we sorted this population from young IgM or Ccr6 KO mice and performed bulk RNAseq

2023-08-28 | GSE236072 | GEO

Thymic mimetic cells function beyond self-tolerance [mimetics]

Project description:To examine the transcriptome of various mimetic thymic epithelial cell populations (CilTEC, MyoTEC, Hetero-post TEC, microfold TEC, endocrine TEC and corneoTEC) we sorted these populations from young WT mice and performed bulk RNAseq

2023-08-28 | GSE236070 | GEO

Thymic mimetic cells function beyond self-tolerance [scATAC-Seq Multiome]

Project description:Deliniating thymic epithelial cell heterogeneity by combined single cell RNAseq and ATACseq

2023-08-28 | GSE236667 | GEO

Thymic mimetic cells function beyond self-tolerance [scRNA-Seq Spib chimeras]

Project description:Deliniating the antigen-presenting compartment of thymic Spib–/– and Spib+/– chimeric mice

2023-08-28 | GSE236669 | GEO

Thymic mimetic cells function beyond self-tolerance

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-08-27 | GSE236075 | GEO

LC-MSMS of the MHC-I immunopeptidome of murine thymic epithelial cells

Project description:Antigen presentation by cortical and medullary thymic epithelial cells (cTEC and mTEC) ensures the formation of a self-restricted and self-tolerant T cell repertoire, respectively. As such, a broad diversity of self-antigens needs to be presented by mTEC to induce T cell’s self-tolerance. Even though the expression and antigen presentation of protein coding genes in mTEC has been abundantly described, little is known of the implication of allegedly noncoding regions of the genome to tolerance induction. In this study, we focused on transposable elements (TE), which have been shown to be highly expressed by mTEC.

2024-04-17 | PXD042241 | Pride

Ikaros is a principal regulator of Aire+ mTEC homeostasis, thymic mimetic cell diversity, and central tolerance (scRNA seq)

Project description:The zinc-finger transcription factor Ikaros (Ikzf1) modulates key gene expression programs important for hematopoietic development, and coding mutations in IKZF1 are found in patients with immunodeficiency, leukemia, and autoimmunity. While Ikaros has a well-established function in hematopoiesis, its role in other cell types is less well defined. Here, we uncover new functions for Ikaros in thymic epithelial lineage development and show that Ikzf1 expression in medullary thymic epithelial cells (mTECs) is required for both Autoimmune Regulator positive (Aire+) mTEC development and tissue-specific antigen (TSA) gene expression. Accordingly, TEC-specific deletion of Ikzf1 in mice results in a profound decrease in Aire+ mTECs, a global loss of TSA gene expression, and the development of autoimmunity. Moreover, Ikaros shapes thymic mimetic cell diversity and its deletion results in a dramatic expansion of thymic tuft cells and muscle-like mTECs and a loss of other Aire-dependent mimetic populations. Single-cell analysis reveals Ikaros modulates core transcriptional programs in TECs that correlate with the observed cellular changes. Our findings highlight a previously undescribed role for Ikaros in regulating epithelial lineage development and function, and suggest that failed thymic central tolerance could contribute to the autoimmunity seen in humans with IKZF1 mutations.

2023-10-25 | GSE241742 | GEO

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