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)derived 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.
TOX2 regulates human natural killer cell development by controlling T-BET expression.
Specimen part, Subject
View SamplesA small subset of T cells also expresses kiler-cell immunoglobulin-like receptors (KIRs). We find that KIR+ T cells primarily reside in the CD56+ T population. However, little is known on how these cells are different from the conventional CD56- T, NK, and iNKT cells.
Multiplex and genome-wide analyses reveal distinctive properties of KIR+ and CD56+ T cells in human blood.
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View SamplesPBMC from house dust mite (HDM) sensitized atopics with or without asthma (or nonallergic controls) were cultured in the presence or absence of HDM extract for 24 hours.
Differential gene network analysis for the identification of asthma-associated therapeutic targets in allergen-specific T-helper memory responses.
Specimen part, Disease stage, Subject
View SamplesARC (NSC 188491, SMA-491), 4-amino-6-hydrazino-7-beta-d-ribofuranosyl-7H-pyrrolo-(2,3-d)-pyrimidine-5-carboxamide, is a nucleoside analog with profound in vitro anti-cancer activity. First identified in a high-throughput screen for inhibitors of p21 mRNA expression, subsequent experiments showed that ARC also repressed expression of hdm2 and survivin, leading to its classification as a global inhibitor of transcription 1. The following Hu U133 plus 2.0 arrays represent single time point (24 hour) gene expression analysis of transcripts altered by ARC treatment. Arrays for the other compounds (sangivamycin and doxorubicin) are included as comparators.
ARC (NSC 188491) has identical activity to Sangivamycin (NSC 65346) including inhibition of both P-TEFb and PKC.
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View SamplesGene expression analysis under normal culture conditions (RPMI-10%FBS) and at optimal cell densities.
Low-risk susceptibility alleles in 40 human breast cancer cell lines.
Cell line
View SamplesPBMC from house dust mite (HDM) sensitized atopics were cultured in the presence or absence of HDM extract for 24 hours.
Distinguishing benign from pathologic TH2 immunity in atopic children.
No sample metadata fields
View SamplesETS1 and RAS/ERK regulate a common gene expression program in establishing enviroment suitable for prostate cancer cell migration. Overall design: mRNA profiles of luciferase knockdown (WT), ETS1 knockdown, and U0126 treated DU145 cells were generated using deep sequencing, in triplicate, using Illumina HiSeq. Knockdowns were stable shRNA expression from a lentiviral construct selected with puromycin.
Interaction with ZMYND11 mediates opposing roles of Ras-responsive transcription factors ETS1 and ETS2.
No sample metadata fields
View SamplesAnalysis of expression profiles of human pDC cell line (CAL1) compared to an immature T cell line (MOLT4)
Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development.
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View SamplesAnalysis of expression profiles of pDCs from wild type and heterozygous E2-2 mice. Results show the control by E2-2 of the expression of pDC-enriched genes.
Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development.
No sample metadata fields
View SamplesLoss of E2F transcription factos alters metastatic capacity of MMTV-PyMT tumors.
Histological subtypes of mouse mammary tumors reveal conserved relationships to human cancers.
Disease
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