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Stepwise chromatin and transcriptional acquisition of an intraepithelial lymphocyte program

ABSTRACT: Stepwise chromatin and transcriptional acquisition of an intraepithelial lymphocyte program

PROVIDER: PRJNA610060 | ENA |

REPOSITORIES: ENA

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Stepwise chromatin and transcriptional acquisition of an intraepithelial lymphocyte program

Project description:Mesenteric lymph node (mLN) T cells undergo tissue adaptation upon migrating to intestinal lamina propria (LP) and intraepithelial (IE) compartments, ensuring appropriate balance between tolerance and resistance. By combining mouse genetics with single-cell and chromatin analyses, we addressed the molecular imprinting of gut epithelium on T cells. Transcriptionally, conventional and regulatory (Treg) CD4+ T cells from mLN, LP and IE segregate based on the gut layer they occupy; trajectory analysis suggests a stepwise loss of CD4-programming and acquisition of an intraepithelial profile. Treg fate–mapping coupled with RNA– and ATAC–sequencing revealed that the Treg program shuts down before an intraepithelial program becomes fully accessible at the epithelium. Ablation of CD4 lineage–defining transcription factor ThPOK results in premature acquisition of an IEL profile by mLN Tregs, partially recapitulating epithelium imprinting. Thus, coordinated replacement of circulating lymphocyte program with site–specific transcriptional and chromatin changes is necessary for tissue imprinting.

2021-01-04 | GSE146292 | GEO

Stepwise chromatin and transcriptional acquisition of an intraepithelial lymphocyte program.

Project description: Not available

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Microglia development follows a stepwise program to regulate brain homeostasis

Project description:Microglia development follows a stepwise program to regulate brain homeostasis

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Microglia development follows a stepwise program to regulate brain homeostasis - ChIP-seq

Project description:Microglia play important roles in life-long brain maintenance and in pathology, but are also crucial in the developing central nervous system; yet their regulatory dynamics during development have not been fully elucidated. Genome-wide chromatin and expression profiling coupled with single-cell transcriptomic analysis throughout development reveal that microglia undergo three temporal developmental stages in synchrony with the brain: early, pre-, and adult microglia, which are under the control of distinct regulatory circuits. Knockout of the transcription factor MafB caused disruption of homeostasis in adulthood and increased inflammation. Environmental perturbations, such as the microbiome or prenatal immune activation, led to dysregulation of the developmental program, particularly in terms of inflammation. Together, our work identifies a stepwise developmental program of microglia integrating immune response pathways that may be associated with several neurodevelopmental disorders.

2016-07-13 | GSE79816 | GEO

Microglia development follows a stepwise program to regulate brain homeostasis - RNA seq

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Gene expressions of TCRαβ+ CD8αα+ intraepithelial lymphocyte (IELs) in the small intestine with or without Rbpj gene

Project description:Gene expressions of TCRαβ+ CD8αα+ intraepithelial lymphocyte (IELs) in the small intestine with or without Rbpj gene

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miRNA profiling of biliary intraepithelial neoplasia reveals step-wise tumorigenesis in cholangiocarcinoma

Project description:Biliary intraepithelial neoplasia (BilIN) is a common precursor lesion of distal cholangiocarcinoma (dCCA). However, the sequence leading from a single epithelial layer in normal biliary epithelia to intraepithelial precursor lesions and finally to the invasive tumor is poorly understood. Here, we aimed to elucidate key miRNAs involved in this stepwise process and to identify their possible mRNA target genes in distal cholangiocarcinogenesis. As basis of our study, we conducted Laser Capture Microdissection of FFPE tissue sections of 12 patients with distal cholangiocarcinoma. For each patient, we isolated three matched sample sets, including non-neoplastic biliary epithelia, high grade BilIN (grade 3), and invasive dCCA, thereby representing different stages of distal cholangiocarcinogenesis. This resulted in a total of 36 samples. Total RNA was extracted and the expression of ~800 miRNAs was assessed using the Nanostring® technology. Significantly deregulated miRNAs were validated by quantitative RT-PCR. Target genes were identified using miRWalk2.0 and validated by qRT-PCR and Western blot.

2020-08-07 | GSE140001 | GEO

Single cell RNA sequencing identifies the developmental origin of C-Myc dependent T-bet+thymic intraepithelial lymphocyte precursor

Project description:Single cell RNA sequencing identifies the developmental origin of C-Myc dependent T-bet+thymic intraepithelial lymphocyte precursor

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BCL6 is required for the thymic development of TCRαβ+CD8αα+ intraepithelial lymphocyte lineage

Project description:TCRαβ+CD8αα+ intraepithelial lymphocytes (CD8αα+ αβ IELs), a specialized subset of T cells in the gut epithelium, develop from thymic agonist-selected IEL precursors (IELps). The molecular mechanisms underlying the selection and differentiation of this T cell type in the thymus are largely unknown. Here, we found that Bcl6 deficiency in αβ T cells resulted in nearly the absence of CD8αα+ αβ IELs. BCL6 was expressed by approximately 50% of CD8αα+ αβ IELs but the majority thymic PD1+ IELps post agonist selection; its deficiency blocked early IELp generation in the thymus. Moreover, BCL6 expression in IELps was induced by thymic TCR signaling in an ERK-dependent manner. As a result of Bcl6 deficiency, the precursors of IELps among CD4+CD8+ double positive (DP) thymocytes exhibited increased apoptosis during agonist selection, and impaired IELp differentiation and maturation. Taken together, our results elucidate BCL6 as a crucial transcription factor during the thymic development of CD8αα+ αβ IELs.

2024-02-26 | GSE248163 | GEO

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