Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Id proteins suppress E2A-driven iNKT cell development prior to TCR selection [ChIP-seq]

ABSTRACT: Id proteins have been shown to promote the differentiation of conventional αβ and γδT cells, and to suppress the expansion of invariant Natural Killer T (iNKT) cells and innate-like γδNKT within their respective cell lineages. However, it remains to be determined whether Id proteins regulate lineage specification in developing T cells that give rise to these distinct cell fates. Here we report that in the absence of Id2 and Id3 proteins, E2A prematurely activates genes critical for the iNKT cell lineage prior to TCR expression. Lack of Id proteins also promotes a biased TCR rearrangement in favor of iNKT cell fate prior to selection at the CD4+CD8+ double positive (DP) stage. Enhanced iNKT development in Id3-deficient mice lacking γδNKT cells suggests that Id3 regulates the lineage competition between these populations. RNA-Seq analysis establishes E2A as the transcriptional regulator of both iNKT and γδNKT development. In the absence of pre-TCR signaling, Id2/Id3 deletion gives rise to a large population of iNKT cells and a unique innate-like DP population, despite the block in conventional αβ T cell development. The transcriptional profile of these unique DP cells reflects enrichment of innate-like signature genes, including PLZF (Zbtb16) and Granzyme A (Gzma). Results from these genetic models and genome-wide analyses suggest that Id proteins suppress E2A-driven innate-like T cell programs prior to TCR selection to enforce predominance of conventional T cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE89847 | GEO | 2018/01/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Id proteins suppress E2A-driven iNKT cell development prior to TCR selection [RNA-seq]

Project description:Id proteins have been shown to promote the differentiation of conventional αβ and γδT cells, and to suppress the expansion of invariant Natural Killer T (iNKT) cells and innate-like γδNKT within their respective cell lineages. However, it remains to be determined whether Id proteins regulate lineage specification in developing T cells that give rise to these distinct cell fates. Here we report that in the absence of Id2 and Id3 proteins, E2A prematurely activates genes critical for the iNKT cell lineage prior to TCR expression. Lack of Id proteins also promotes a biased TCR rearrangement in favor of iNKT cell fate prior to selection at the CD4+CD8+ double positive (DP) stage. Enhanced iNKT development in Id3-deficient mice lacking γδNKT cells suggests that Id3 regulates the lineage competition between these populations. RNA-Seq analysis establishes E2A as the transcriptional regulator of both iNKT and γδNKT development. In the absence of pre-TCR signaling, Id2/Id3 deletion gives rise to a large population of iNKT cells and a unique innate-like DP population, despite the block in conventional αβ T cell development. The transcriptional profile of these unique DP cells reflects enrichment of innate-like signature genes, including PLZF (Zbtb16) and Granzyme A (Gzma). Results from these genetic models and genome-wide analyses suggest that Id proteins suppress E2A-driven innate-like T cell programs prior to TCR selection to enforce predominance of conventional T cells.

2018-01-23 | GSE89848 | GEO

Id proteins suppress E2A-driven iNKT cell development prior to TCR selection [RNA-seq_new]

2018-01-23 | GSE100601 | GEO

Id proteins suppress E2A-driven iNKT cell development prior to TCR selection

Project description:Id proteins suppress E2A-driven iNKT cell development prior to TCR selection

| PRJNA353589 | ENA

A genetic circuitry linking Id-proteins (Id2 and Id3) and the AKT-FOXO-mTORC1 axis to suppress innate-variant TFH cell development, maintain T cell quiescence and prevent lymphomagenesis.

Project description:It is now well established that the E- and Id-protein axis regulates multiple steps in lymphocyte development. However, it remains unknown as to how E- and Id-proteins mechanistically enforce and maintain the naïve T cell fate. Here we show that Id2 and Id3 suppressed the development and expansion of innate-variant TFH cells. Innate-variant TFH cells required MHC Class I-like signalling and were associated with germinal center B cell development. We found that Id2 and Id3 induced Foxo1 and Foxp1 expression to antagonize the activation of TFH transcription signature. We show that Id2 and Id3 acted upstream of the Hif1a/Foxo/AKT/mTORC1 pathway as well as the c-myc/p19Arf module to control cellular expansion and activation. We found that mice depleted for Id2 and Id3 expression developed colitis and αβ T cell lymphomas. Lymphomas depleted for Id2 and Id3 expression displayed elevated levels of c-myc whereas p19Arf abundance declined. Transcription signatures of Id2- and Id3-depleted lymphomas revealed similarities with genetic deficiencies associated with Burkitt lymphoma. We propose that in response to antigen receptor and/or cytokine signaling the E-Id protein axis modulates the activities of the PI3K-AKT-mTORC1-Hifa and c-myc/p19Arf pathways to control cellular expansion and homeostatic proliferation. RNA-seq data of 5 of wild type CD4SP cells, 3 of wild type Tfh cells, 3 of Id3-/- CD4SP cells, 3 of Id2-/-Id3-/-(dKO) CD4SP cells, and 6 of Id2-/-Id3-/- lymphoma cells.

2015-03-04 | E-GEOD-64779 | biostudies-arrayexpress

Opposing roles of E2A and Id3 that orchestrate and enforce the naive T cell fate

Project description:It is established that E2A and its antagonist, Id3, modulate developmental progression at the pre-TCR and TCR checkpoints. Here we show at a global scale how E2A promotes commitment to the T cell lineage and how pre-TCR mediated signalling affects E2A genome-wide occupancy. We find aberrant development of CD4 memory-like and TFH-like cells, T-B cell conjugates and, remarkably, B cell follicles in Id3-/-thymi. We also find that Id3-/-CD4 splenocytes exhibit increased numbers of TFH-like cells. We propose a model in which Id3 modulates the naive versus effector/memory cell fate. Collectively, these data show how E2A acts globally to orchestrate T-lineage development and that Id3 antagonizes E2A activity beyond the pre-TCR checkpoint to enforce the naive T cell fate. ChIP-Seq was performed in thymocytes isolated from either untreated Rag2-/-mice (DN3 cells) or Rag2-/- mice injected with anti-CD3e antibody (DN4 cells). ChIP used antibodies against either E2A or H3K4me1.

2011-07-31 | E-GEOD-30518 | biostudies-arrayexpress

Gene expression in neonatal NKT cells and lymphoma samples from mice with high E protein levels [Microarray Expression]

Project description:Inhibitor of DNA binding proteins (ID), including Id1-4, are transcriptional regulators involved in promoting cell proliferation and survival in various cell types. Although upregulation of Id proteins have been widely reported to be associated with a broad spectrum of tumors, recent studies have identified that Id3 also plays a tumor suppressor role in the development of Burkittâ??s lymphoma in humans and Hepatosplenic T cell lymphomas in mice. However, there is a lack of evidence to suggest the tumor suppressor roles for other Id genes, particularly Id2, which is highly expressed in many T lymphocytes. In this study we report that Id2 plays a tumor suppressive role in collaboration with Id3 in developing T cells in mice. We found that there was rapid lymphoma development in Id2f/fId3f/fLckCre mice caused by unchecked neonatal expansion of invariant Natural Killer T (iNKT) cells and a unique subset of innate-like, CD1d-independent T cells. These tumors also gave rise to lymphomas in Rag-deficient mice, reaffirming the inherent tumorigenic potential of these cells. Microarray analysis revealed a significantly modified program in expanding iNKT cells that ultimately contributed to tumorigenesis. We found chromosome instability and significant upregulation of several different signaling pathways, including pathways for multiple chemokines, cytokines and their receptors, in these tumors. While Id proteins are being considered as potential therapeutic targets in some cancer models, our results highlight the possibility of aggravated tumorigenesis upon suppression of Id2 and Id3. Pre-malignant iNKT (TCRÎ²+CD1dTet+) cells were sorted from three 20 day old L-DKO mice. Lymphoma cells (T cells that are CD1dTet+ or CD1dTet-) were sorted from tissues of 18-37 week old L-DKO mice. Total RNA was extracted, and mRNA profiling was done using GeneChip Mouse Genome 430A 2.0 arrays (GPL8321, Affymetrix)

2017-04-20 | E-GEOD-73864 | biostudies-arrayexpress

Opposing roles of E2A and Id3 that orchestrate and enforce the naive T cell fate

2011-07-31 | GSE30518 | GEO

Mus musculus

Project description:Id proteins suppress E2A-driven iNKT cell development prior to TCR selection [RNA-seq_new]

| PRJNA392277 | ENA

Mus musculus

Project description:Id proteins suppress E2A-driven iNKT cell development prior to TCR selection [RNA-seq]

| PRJNA354280 | ENA

Mus musculus

Project description:Id proteins suppress E2A-driven iNKT cell development prior to TCR selection [ChIP-seq]

| PRJNA354281 | ENA