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ATAC-seq and RNA-seq of hematopoietic progenitor cells (HPC) and Natural Killer (NK) cells transduced with transcription factors T-BET or EOMES

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

ORGANISM(S): Homo sapiens

PROVIDER: GSE166439 | GEO | 2021/08/27

REPOSITORIES: GEO

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Transcriptome profiling of hematopoietic progenitor cells (HPC) transduced with transcription factors T-BET or EOMES

Project description:T-BET and EOMES are key transcription factors in the development of mature Natural Killer (NK) cells in mice. However, the role of these transcription factors during human NK cell development is less well understood. Therefore, we overexpressed T-BET or EOMES in human umbilical cord blood-derived HPC and cultured them in vitro in an NK cell differentiation model. To evaluate the effect of early overexpression of T-BET and EOMES in HPC, transcriptome profiling was performed on T-BET and EOMES overexpressing HPC and compared to control transduced HPC by RNA sequencing on day 0 of culture.

2021-08-27 | GSE166437 | GEO

Profiling of the chromatin landscape of hematopoietic progenitor cells (HPC) transduced with transcription factors T-BET and EOMES [ATAC-seq HPC]

Project description:T-BET and EOMES are key transcription factors in the development of mature Natural Killer (NK) cells in mice. However, the role of these transcription factors during human NK cell development is less well understood. Therefore, we overexpressed T-BET or EOMES in human umbilical cord blood-derived HPC and cultured them in vitro in an NK cell differentiation model. To evaluate the effect of early overexpression of T-BET and EOMES in HPC, the chromatin landscape was uncovered using assay for transposase-accessible chromatin (ATAC) sequencing. In this way, the regulatory effect of T-BET and EOMES overexpression on the epigenome of HPC was evaluated.

2021-08-27 | GSE166435 | GEO

The transcription factors T-bet and Eomes control key checkpoints of natural killer cell maturation.

Project description:Natural killer (NK) cells play critical roles defending against tumors and pathogens. We show that mice lacking both transcription factors Eomesodermin (Eomes) and T-bet failed to develop NK cells. Developmental stability of immature NK cells constitutively expressing the death ligand TRAIL depended on T-bet. Conversely, maturation characterized by loss of constitutive TRAIL expression and induction of Ly49 receptor diversity and integrin CD49b (DX5(+)) required Eomes. Mature NK cells from which Eomes was deleted reverted to phenotypic immaturity if T-bet was present or downregulated NK lineage antigens if T-bet was absent, despite retaining expression of Ly49 receptors. Fetal and adult hepatic hematopoiesis restricted Eomes expression and limited NK development to the T-bet-dependent, immature stage, whereas medullary hematopoiesis permitted Eomes-dependent NK maturation in adult mice. These findings reveal two sequential, genetically separable checkpoints of NK cell maturation, the progression of which is metered largely by the anatomic localization of hematopoiesis.

| S-EPMC3381976 | biostudies-literature

ATAC-seq and RNA-seq of hematopoietic progenitor cells (HPC) and Natural Killer (NK) cells transduced with transcription factors T-BET or EOMES

Project description:ATAC-seq and RNA-seq of hematopoietic progenitor cells (HPC) and Natural Killer (NK) cells transduced with transcription factors T-BET or EOMES

| PRJNA700964 | ENA

Transcriptome profiling of human Natural Killer (NK) cells overexpressing the transcription factors T-BET or EOMES

Project description:T-BET and EOMES are key transcription factors in the development of mature NK cells in mice. However, the role of these transcription factors during human NK cell development is less well understood. Therefore, we overexpressed T-BET or EOMES in human umbilical cord blood-derived hematopoietic progenitor cells (HPC) and cultured them in vitro in an NK cell differentiation model. On day 21 of culture mature stage 4 (CD56+CD94+CD16-) and stage 5 (CD56+CD94+CD16+) NK cells from T-BET or EOMES overexpression and control cultures were sorted, whereafter mRNA was isolated and transcriptome analysis was performed by RNA sequencing. Evaluation of the transcriptome in mature NK cells with T-BET or EOMES overexpression could reveal the molecular mechanisms of how T-BET and EOMES play a role in terminal NK cell maturation.

2021-08-27 | GSE166438 | GEO

Transcriptome profiling of hematopoietic progenitor cells (HPC) transduced with transcription factors T-BET or EOMES

Project description:Transcriptome profiling of hematopoietic progenitor cells (HPC) transduced with transcription factors T-BET or EOMES

| PRJNA700968 | ENA

Sequential actions of EOMES and T-BET promote stepwise maturation of natural killer cells.

Project description:EOMES and T-BET are related T-box transcription factors that control natural killer (NK) cell development. Here we demonstrate that EOMES and T-BET regulate largely distinct gene sets during this process. EOMES is dominantly expressed in immature NK cells and drives early lineage specification by inducing hallmark receptors and functions. By contrast, T-BET is dominant in mature NK cells, where it induces responsiveness to IL-12 and represses the cell cycle, likely through transcriptional repressors. Regardless, many genes with distinct functions are co-regulated by the two transcription factors. By generating two gene-modified mice facilitating chromatin immunoprecipitation of endogenous EOMES and T-BET, we show a strong overlap in their DNA binding targets, as well as extensive epigenetic changes during NK cell differentiation. Our data thus suggest that EOMES and T-BET may distinctly govern, via differential expression and co-factors recruitment, NK cell maturation by inserting partially overlapping epigenetic regulations.

| S-EPMC8440589 | biostudies-literature

T-BET and EOMES Accelerate and Enhance Functional Differentiation of Human Natural Killer Cells.

Project description:T-bet and Eomes are transcription factors that are known to be important in maturation and function of murine natural killer (NK) cells. Reduced T-BET and EOMES expression results in dysfunctional NK cells and failure to control tumor growth. In contrast to mice, the current knowledge on the role of T-BET and EOMES in human NK cells is rudimentary. Here, we ectopically expressed either T-BET or EOMES in human hematopoietic progenitor cells. Combined transcriptome, chromatin accessibility and protein expression analyses revealed that T-BET or EOMES epigenetically represses hematopoietic stem cell quiescence and non-NK lineage differentiation genes, while activating an NK cell-specific transcriptome and thereby drastically accelerating NK cell differentiation. In this model, the effects of T-BET and EOMES are largely overlapping, yet EOMES shows a superior role in early NK cell maturation and induces faster NK receptor and enhanced CD16 expression. T-BET particularly controls transcription of terminal maturation markers and epigenetically controls strong induction of KIR expression. Finally, NK cells generated upon T-BET or EOMES overexpression display improved functionality, including increased IFN-γ production and killing, and especially EOMES overexpression NK cells have enhanced antibody-dependent cellular cytotoxicity. Our findings reveal novel insights on the regulatory role of T-BET and EOMES in human NK cell maturation and function, which is essential to further understand human NK cell biology and to optimize adoptive NK cell therapies.

| S-EPMC8497824 | biostudies-literature

Profiling of the chromatin landscape of human natural killer (NK) cells overexpressing the transcription factors T-BET or EOMES

Project description:T-BET and EOMES are key transcription factors in the development of mature NK cells in mice. However, the role of these transcription factors during human NK cell development is less well understood. Therefore, we overexpressed T-BET or EOMES in human umbilical cord blood-derived hematopoietic progenitor cells (HPC) and cultured them in vitro in an NK cell differentiation model. On day 21 of culture mature stage 4 (CD56+CD94+CD16-) and stage 5 (CD56+CD94+CD16+) NK cells from T-BET or EOMES overexpression and control cultures were sorted, whereafter genomic DNA was isolated and the chromatin accessibility landscape was determined by assay for transposase-accessible chromatin (ATAC) sequencing. Profiling of the epigenetic changes during T-BET or EOMES overexpression in mature NK cells revealed new insights in the regulatory role of T-BET and EOMES during terminal NK cell maturation.

2021-08-27 | GSE166436 | GEO

Profiling of the chromatin landscape of hematopoietic progenitor cells (HPC) transduced with transcription factors T-BET and EOMES [ATAC-seq HPC]

Project description:Profiling of the chromatin landscape of hematopoietic progenitor cells (HPC) transduced with transcription factors T-BET and EOMES [ATAC-seq HPC]

| PRJNA700965 | ENA

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