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GATA3 restrains Notch signaling activity and represses NK cell development to induce human T cell commitment following Notch-induced T-lineage specification

ABSTRACT: GATA3 restrains Notch signaling activity and represses NK cell development to induce human T cell commitment following Notch-induced T-lineage specification

PROVIDER: PRJNA292005 | ENA |

REPOSITORIES: ENA

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GATA3 restrains Notch signaling activity and represses NK cell development to induce human T cell commitment following Notch-induced T-lineage specification (ChIP-Seq)

Project description:The stepwise conversion of multipotent precursors into committed T-cell progenitors depends on several transcriptional regulators, but the interplay between these factors is still obscure. This is particularly true in human since the core early Notch signalling pathway also supports NK cell development and requires tight regulation for efficient T-lineage commitment and differentiation. Here, we show that GATA3, in contrast to TCF1, induces T-lineage commitment following NOTCH1-induced T-lineage specification through direct regulation of at least 3 distinct processes: repression of NK-cell fate, activation of T-lineage genes to promote further differentiation, and downmodulation of Notch signalling activity. GATA3-mediated repression of the NOTCH1 target gene DTX1 hereby is essential to induce T-lineage commitment at the expense of NK cell differentiation. Thus, human T-lineage commitment is dependent on the precise collaboration of several transcriptional regulators that integrate through both positive and negative regulatory loops. ChIP-sequencing data was generated for GATA3 in human thymocytes

2016-04-06 | E-GEOD-71751 | biostudies-arrayexpress

GATA3 restrains Notch signaling activity and represses NK cell development to induce human T cell commitment following Notch-induced T-lineage specification (expression)

Project description:The stepwise conversion of multipotent precursors into committed T-cell progenitors depends on several transcriptional regulators, but the interplay between these factors is still obscure. This is particularly true in human since the core early Notch signalling pathway also supports NK cell development and requires tight regulation for efficient T-lineage commitment and differentiation. Here, we show that GATA3, in contrast to TCF1, induces T-lineage commitment following NOTCH1-induced T-lineage specification through direct regulation of at least 3 distinct processes: repression of NK-cell fate, activation of T-lineage genes to promote further differentiation, and downmodulation of Notch signalling activity. GATA3-mediated repression of the NOTCH1 target gene DTX1 hereby is essential to induce T-lineage commitment at the expense of NK cell differentiation. Thus, human T-lineage commitment is dependent on the precise collaboration of several transcriptional regulators that integrate through both positive and negative regulatory loops. Gene expression was profiled in CT CD34+ cells after transduction with control or GATA3 and coculture on OP9-DL1 for 48h. Cells were collected 48h after coculture and sorted for CD45+EGFP+. 3 independent experiments were performed on 3 different thymus donors.

2016-04-06 | E-GEOD-71752 | biostudies-arrayexpress

GATA3 restrains Notch signaling activity and represses NK cell development to induce human T cell commitment following Notch-induced T-lineage specification (expression)

2016-04-06 | GSE71752 | GEO

GATA3 restrains Notch signaling activity and represses NK cell development to induce human T cell commitment following Notch-induced T-lineage specification (ChIP-Seq)

2016-04-06 | GSE71751 | GEO

GATA3 induces human T cell commitment following Notch-induced T-lineage specification (expression)

2016-04-06 | GSE76348 | GEO

GATA3 induces human T cell commitment following Notch-induced T-lineage specification (expression)

Project description:Here, we show that GATA3 induces T-lineage commitment following Notch-induced T-lineage specification through direct regulation of at least 3 distinct processes: repression of NK-cell fate, activation of T-lineage genes to promote further differentiation, and down modulation of Notch signalling activity. Gene expression was measured in RPMI8402 cells after transduction with control, shGATA3 or shTCF1 and culture for 48h. Cells were collected 48h after transduction and sorted for EGFP+. This was performed for 2 replicates.

2016-04-06 | E-GEOD-76348 | biostudies-arrayexpress

Expression data from Gata3+/- and Gata3-/- ESC-derived T-cell progenitors

Project description:GATA3 plays a crucial role during early T-cell development and also dictates later T-cell differentiation outcomes. However, its role and collaboration with the Notch signaling pathway in the induction of T-lineage specification and commitment have not been fully elucidated. We show that GATA3 deficiency in hematopoietic progenitors results in an early block in T-cell development despite the presence of Notch signals, with a failure to up-regulate Bcl11b expression, leading to a diversion toward myeloid lineage fate. GATA3 deficiency results in dysregulated Cdkn2b expression, leading to apoptosis of early T-lineage cells due to inhibition of CDK4/6 function. We also show that GATA-3 induces Bcl11b, and together with Bcl11b represses Cdkn2b expression. Our findings provide a signaling and transcriptional network by which the T-lineage program in response to Notch signals is realized.

2022-05-01 | GSE199279 | GEO

GATA3 restrains Notch signaling activity and represses NK cell development to induce human T cell commitment following Notch-induced T-lineage specification

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-04-06 | E-GEOD-71753 | biostudies-arrayexpress

ILC2 development requires GATA3-related super-enhancers after lineage commitment

Project description:ILC2 development requires GATA3-related super-enhancers after lineage commitment

| PRJNA902420 | ENA

GATA3 restrains Notch signaling activity and represses NK cell development to induce human T cell commitment following Notch-induced T-lineage specification

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

2016-04-06 | GSE71753 | GEO