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NF-κB-induced expression of T-bet suppresses proliferation of malignant B cells and is associated with good prognosis in chronic lymphocytic leukemia [scATAC-seq]

ABSTRACT: The T-box transcription factor T-bet is encoded by Tbx21 and was identified to play a role in aging and tissue localization of B cells. T-bet expression was detected in malignant B cells but its potential role in B-cell malignancies remains largely unexplored. We used single cell RNA sequencing (scRNA-seq) and the assay for transposase accessible chromatin using sequencing (scATAC-seq) to analyze the regulatory role of T-bet in TCL1 leukemia.

ORGANISM(S): Mus musculus

PROVIDER: GSE234224 | GEO | 2024/06/01

REPOSITORIES: GEO

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NF-κB-induced expression of T-bet suppresses proliferation of malignant B cells and is associated with good prognosis in chronic lymphocytic leukemia [scRNA-seq]

Project description:The T-box transcription factor T-bet is encoded by Tbx21 and was identified to play a role in aging and tissue localization of B cells. T-bet expression was detected in malignant B cells but its potential role in B-cell malignancies remains largely unexplored. We used single cell RNA sequencing (scRNA-seq) and the assay for transposase accessible chromatin using sequencing (scATAC-seq) to analyze the regulatory role of T-bet in TCL1 leukemia.

2024-06-01 | GSE234225 | GEO

NF-κB-induced expression of T-bet suppresses the proliferation of malignant B cells and is associated with good prognosis in chronic lymphocytic leukemia

Project description:Tbx21-/- TCL1 cells were generated to explore the effect of T-bet expression in malignant B cells. Single-cell suspensions from spleens of Tbx21 knockout and control TCL1 mice were prepared and splenocytes were enriched in TCL1 cells, resulting in a purity above 97% of CD5+ CD19+ cells. RNA sequencing libraries were prepared using the Illumina TruSeq Stranded mRNA Kit and sequenced on the Illumina NovaSeq 6000.

2024-01-31 | E-MTAB-13030 | biostudies-arrayexpress

NF-κB-induced expression of T-bet suppresses proliferation of malignant B cells and is associated with good prognosis in chronic lymphocytic leukemia [scATAC-seq]

Project description:NF-κB-induced expression of T-bet suppresses proliferation of malignant B cells and is associated with good prognosis in chronic lymphocytic leukemia [scATAC-seq]

| PRJNA980577 | ENA

The Transcription Factor T-bet Is Induced by Multiple Pathways and Prevents an Endogenous Th2 Cell Program during Th1 Cell Responses

Project description:T-bet is a critical transcription factor for T helper 1 (Th1) cell differentiation. To study the regulation and functions of T-bet, we developed a T-bet-ZsGreen reporter mouse strain, in which GFP faithfully reflects the expression of T-bet. By using this tool, we report that signals elicited by IL-12 and IFNg are redundant in inducing T-bet in mice infected with Toxoplasma gondii and that T-bet does not contribute to its own expression when induced by IL-12 and IFNg. While both T-bet and Stat4 are critical for IFNg production, IFNg signaling is dispensable. Strikingly, loss of T-bet results in activation of an endogenous Th2 program in cells expressing T-bet-ZsGreen. Genome-wide analyses suggest T-bet directly induces Th1-related genes but indirectly suppresses Th2-related genes. Our study revealed redundancy and synergy among several Th1-inducing pathways in regulating the expression of T-bet and IFNg, and a critical role of T-bet in suppressing an endogenous Th2 program. RNA-Seq experiments were performed using total RNAs isolated from both wild type and Tbx21-/- Th1 cells in duplicates. Tbet ChIP-seq was performed using wild type Th1 cells. H3K4me1 and H3K27me3 ChIP-seq was performed using both wild type and Tbx21-/- Th1 cells.

2012-10-04 | E-GEOD-38808 | biostudies-arrayexpress

scATAC-seq of mouse Plasmodium-specific CD4+ T cells

Project description:Plasmodium-specific CD4+ T cells from mice infected with Plasmodium chabaudi chabaudi AS parasites were recovered at Days 0, 4, 7, and 32 to undergo processing and to generate scATAC-seq dataset. At Day 7, CXCR5+ and CXCR6+ cells were recovered separately. At Day 32, mice were administered with either saline or artesunate (intermittent artesunate therapy - IAT). scATAC-seq dataset was analysed to investigate epigenomic landscapes of CD4+ T cells from effector to memory states.

2020-10-14 | E-MTAB-9402 | biostudies-arrayexpress

scATAC-seq of early brain organoid development from pluripotency

Project description:To study developmental trajectories in brain organoids, we conducted scRNA-seq and scATAC-seq in parallel on a dense timecourse of early development.

2022-08-18 | E-MTAB-11998 | biostudies-arrayexpress

NF-κB-induced expression of T-bet suppresses proliferation of malignant B cells and is associated with good prognosis in chronic lymphocytic leukemia

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

2024-06-01 | GSE234226 | GEO

High levels of CD20 expression predict good prognosis in chronic lymphocytic leukemia.

Project description:Heterogeneity of CD20 expression exists in chronic lymphocytic leukemia (CLL), therefore, we explored the prognostic significance of CD20 expression in Chinese patients with CLL. Multiparameter flow cytometry was used to detect the expression of CD20 in CD5(+) CD19(+) cells. In 172 CLL patients, the median expression percent of CD20 was 97.82% (range, 0-100), and the median mean fluorescence intensity (MFI) of CD20 in CLL cells was 731.45 (range, 0.00-9071.90). The percentage of CD20(+) cells in the patient group with mutated variable region of immunoglobulin genes (IGHV) was higher than in the non-mutant IGHV group (mean, 92.1% vs 80.4%, P < 0.001). There were no differences in the MFI of CD20(+) cells in all prognostic factor groups. Representation of the data using a receiver operating characteristic plot reflected separation between the two IGHV groups, with an area under the curve of 0.661 (95% confidence interval, 0.569-0.753). At the cut-off value of 60.3% for percentage of CD20, the sensitivity and specificity were 90.00% and 38.46%, respectively. Patients whose percentage of CD20 antigen was above 60.3% had longer treatment-free survival (hazard ratio, 0.452; 95% confidence interval, 0.232-0.884, P = 0.020). Percentage and MFI of CD20 were the variables not associated with treatment-free survival by multivariate Cox regression analysis (P < 0.05). High level of CD20 expression in de novo CLL appears to be associated with a good prognosis.

| S-EPMC7657116 | biostudies-literature

Differential Regulation of Transcription Factor T-bet Induction during NK Cell Development and Th1 Cell Differentiation

Project description:Adaptive CD4 T helper cells and their innate counterparts, innate lymphoid cells, utilize an identical set of lineage-determining transcription factors (LDTFs) for their differentiation and functions. However, the similarities and differences in the induction of the LDTFs in these lymphocytes are still elusive. Here we show that type 1 T helper (Th1) cells and natural killer (NK) cells displayed distinct epigenomes at the Tbx21 locus, which encodes T-bet, the LDTF for type 1 lymphocytes. The initial induction of T-bet in NK precursors was partially dependent on the NK-specific DNase I hypersensitive site Tbx21-CNS-3 and the expression of IL-18 receptor; IL-18 induced T-bet expression through RUNX3, which binds to Tbx21-CNS-3. By contrast, Tbx21-CNS-12 containing STAT binding motifs was critical for IL-12-induced T-bet expression during Th1 cell differentiation both in vitro and in vivo. Thus, innate and adaptive lymphocytes of same class may utilize distinct enhancer elements for their development and differentiation.

2022-02-03 | GSE172358 | GEO

TOX2 regulates human natural killer cell development by controlling T-BET expression

Project description:Thymocyte selection-associated high mobility group box protein family member 2 (TOX2) is a transcription factor belonging to the TOX family that shares a highly conserved high mobility group DNA binding domain with the other TOX members. While TOX1 has been shown to be an essential regulator of T-cell and natural killer (NK) cell differentiation in mice, little is known about the roles of the other TOX family members in lymphocyte development, particularly in humans. In this study, we found that TOX2 was preferentially expressed in mature human NK cells and was upregulated during in vitro differentiation of NK cells from human umbilical cord blood (UCB)M-bM-^@M-^Sderived CD34+ cells. Gene silencing of TOX2 intrinsically hindered the transition between early developmental stages of NK cells, while overexpression of TOX2 enhanced the development of mature NK cells from UCB CD34+ cells. We subsequently found that TOX2 was independent of ETS-1 but could directly upregulate the transcription of TBX21 (encoding T-BET). Overexpression of T-BET rescued the TOX2 knockdown phenotypes. Given the essential function of T-BET in NK cell differentiation, TOX2 therefore plays a crucial role in controlling normal NK cell development by acting upstream of TBX21 transcriptional regulation. survey of NK cells over time

2014-12-22 | E-GEOD-58589 | biostudies-arrayexpress

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