NF-κB-induced expression of T-bet suppresses the proliferation of malignant B cells and is associated with good prognosis in chronic lymphocytic leukemia
Ontology highlight
ABSTRACT: 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.
Project description:The function of ID4 in CLL development was studied in vivo using TCL1 transgenic mouse model that develop leukemia similar to human CLL. TCL1 mice with ID4 single knockout gene have accelerated CLL progression. Results from the animal study suggest ID4 as a tumor suppressor gene that might regulate cell proliferation and apoptosis in B lymphocytes. Gene expression in CD19-positive splenic B cells collected from 1-month old ID4+/-TCL1-tg and ID4+/+TCL1-tg mice was compared by microarray, the goal is to find ID4-regulated genes involved in CLL development.
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.
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.
Project description:POU transcription factor Pou5f1 (Oct3/4) is required to maintain ES cells in an undifferentiated state. Here we show that global expression profiling of Oct3/4-manipulated ES cells delineates the downstream target genes of Oct3/4. Combined with data from genome-wide chromatin-immunoprecipitation assays, this analysis identifies not only primary downstream targets of Oct3/4, but also secondary or tertiary targets. Furthermore, the analysis also reveals that downstream target genes are regulated either positively or negatively by Oct3/4. Identification of a group of genes that show both activation and repression depending on Oct3/4 expression levels provides a possible mechanism for the requirement of appropriate Oct3/4 expression to maintain undifferentiated ES cells. As a proof-of-principle study, one of the downstream genes, Tcl1, has been analyzed in detail. We show that Oct3/4 binds to the promoter region of Tcl1 and activates its transcription. We also show that Tcl1 is involved in the regulation of proliferation, but not differentiation, in ES cells. These findings suggest that the global expression profiling of gene-manipulated ES cells can help to delineate the structure and dynamics of gene regulatory networks.
Project description:Tcl1 is known to be involved in survival, proliferation and differentiation of human lymphocytes and mouse embryonic stem cells. Loss of Tcl1 gene in the KO mouse model affects skin integrity inducing alopecia and ulcerations. The study used epidermal keratinocytes from wild type (WT), Tcl1 knock down (KO) and K14-driven TCL1 transgenic (TGKO) mouse models to investigate the role of Tcl1 gene in the skin homeostasis. Our data indicate that Tcl1 loss mainly induces a decrease in the gene expression of keratinocytes, which is largely rescued by K14-TCL1. GO analysis revealed Tcl1 to be involved in the proliferation and differentiation of mouse keratinocytes. Moreover, pathway analysis identifies growth factor and MAPK signaling to be highly implicated.
Project description:Tcl1 tg mice develop a chronic lymphocytic leukemia (CLL) -like disease. To investigate the contribution of the adhesion molecule CD44 to CLL pathophysiology, we developed a CD19Cre CD44flox/flox Tcl1 tg mouse with a B cell specific CD44 deficiency (CD44ΔB Tcl1 tg). We used the Clariom S mouse microarray from Affymetrix to investigate transcriptional differeneces between Tcl1 tg and CD44ΔB Tcl1 tg mice
Project description:Tcl1 is one of embryonic stem cell specific transcripts identified by digital differential display analysis. Tcl1 is highly expressed during early embryogenesis and to some extent in embryonic stem cells. Its expression in adult tissues is restricted to testis and ovary, and is found to decline if Oct-3/4 expression is suppressed in embryonic stem cells. It is reported that the female knockout mice exhibit reduced fertility. It was first identified in human T-cell tumors and the tumorigenic property was proved by a series of transgenic studies. We have used DNA microarray to identify potential Tcl1 targets in embryonic stem cells and the influence of Tcl1 on stemness. Experiment Overall Design: We analyzed two arrays, each comparing expression profiles of a Tcl1 gene disruptant and a Tcl1 stable transformant. We used different clones with their dyes swapped.(biological replication)
Project description:Transcriptome analysis of RNA samples from leukemia cells of ROR1xTCL1 and TCL1 transgenic mice Animals engrafted with ROR1xTCL1 leukemia-cells developed more aggressive disease than mice engrafted with TCL1 leukemia cells. Transcriptome analysis of RNA samples from leukemia ROR1xTCL1 transgenic mice revealed shared common gene expression signatures that were distinct from those of TCL1 leukemia-cells. We performed microarray transcriptome analyses on isolated leukemia cells that developed in ROR1xTCL1 Tg mice (n=4) or TCL1 Tg mice (n=4) using the Affymetrix Mouse Exon 1.0 ST platform. Array data was processed by Affymetrix Exon Array Computational Tool. No techinical replicates were performed.
Project description:Transcriptome analysis of RNA samples from leukemia cells of ROR1xTCL1 and TCL1 transgenic mice Animals engrafted with ROR1xTCL1 leukemia-cells developed more aggressive disease than mice engrafted with TCL1 leukemia cells. Transcriptome analysis of RNA samples from leukemia ROR1xTCL1 transgenic mice revealed shared common gene expression signatures that were distinct from those of TCL1 leukemia-cells.