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TOX2 coordinates with TET2 to positively regulate central memory differentiation in human CAR T cells

ABSTRACT: To investigate the effects of TOX and TOX2 on memory T cell differentiation in human CAR T cells, we used shRNA to knock down TOX2 or TOX, or overexpress FLAG-TOX2. We then performed gene expression profiling analysis using RNAseq, plus examined the binding of TOX2 to chromatin using ChIPseq.

ORGANISM(S): Homo sapiens

PROVIDER: GSE231620 | GEO | 2023/07/24

REPOSITORIES: GEO

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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

Distruption of TOX and TOX2 transcription factors in CAR T cells limits T cell exhaustion [ATAC-Seq]

Project description:We comapre mRNA expression level TOX and TOX2 CAR TILS and WT CAR TILs

2019-05-31 | GSE130539 | GEO

Distruption of TOX and TOX2 transcription factors in CAR T cells limits T cell exhaustion [RNA-Seq]

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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)–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.

2014-12-22 | GSE58589 | GEO

Genome binding/occupancy profiling of Tox2 in Tfh-like cells

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Transcription factor Tox2 functions to promote chromatin remodeling during T follicular helper (Tfh) cell development (ATAC-seq)

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Global gene expression profile of CD4+ T cells activated and infected with Tox2- or GFP-only virus under different conditions (RNA-Seq)

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Distruption of TOX and TOX2 transcription factors in CAR T cells limits T cell exhaustion

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Transcription Factor Tox2 is required for Follicular Helper T Cells differentiation

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2020-06-01 | GSE136694 | GEO

Distruption of TOX and TOX2 transcription factors in CAR T cells limits T cell exhaustion [RNA-Seq]

Project description:Distruption of TOX and TOX2 transcription factors in CAR T cells limits T cell exhaustion [RNA-Seq]

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