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Transmembrane TNF-TNFR2 axis promotes generation of human T cell precursors.

ABSTRACT: The goal of this study is to dissect the impact of soluble (sTNF) and transmembrane (tmTNF) forms of tumour necrosis factor on the differentiation of human hematopoietic stem and progenitor cells (HSPCs) into T cell precursors. To achieve this, we utilized scRNA-sequencing technologies to compare the transcriptome profiles of HSPCs that had been differentiated in the artificial thymic organoid (ATO) system in the absence (control) or presence of TNF signal (soluble or transmembrane).

ORGANISM(S): Homo sapiens

PROVIDER: GSE211400 | GEO | 2022/12/12

REPOSITORIES: GEO

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Transmembrane TNF-TNFR2 axis promotes generation of human T cell precursors

Project description:The goal of this study is to understand how low level of IRF8 expression promotes the differentiation of human hematopoietic stem and progenitor cells (HSPCs) into T cell precursors. To achieve this, we utilized a construct that encodes IRF8-ERT2 fusion protein where IRF8 activity is tamoxifen-dependent. We extracted genomic DNA from HSPCs that had been co-cultured with OP9-DLL4 stromal cells and tagmented by Tn5 transposase for ATAC-sequencing. This allowed us to determine the impact of low level of IRF8 activity on the chromatin accessibility landscape of differentiating HSPCs. Our analysis found significant opening of chromatin region at the TNF core promoter in the presence of low level of IRF8 activity.

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Transmembrane TNF-TNFR2 axis promotes generation of human T cell precursors

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Transmembrane TNF-TNFR2 axis promotes generation of human T cell precursors

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Generation of mature T cells from human hematopoietic stem/progenitor cells in artificial thymic organoids

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Transmembrane TNF-TNFR2 Impairs Th17 Differentiation by Promoting Il2 Expression.

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