Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The transcription factor Bhlhe40 programs mitochondrial regulation of resident CD8+ T cell fitness and functionality

ABSTRACT: The transcription factor Bhlhe40 programs mitochondrial regulation of resident CD8+ T cell fitness and functionality

PROVIDER: PRJNA558154 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR9887310_1.fastq.gz	Fastqsanger.gz
	SRR9887310_2.fastq.gz	Fastqsanger.gz
	SRR9887311_1.fastq.gz	Fastqsanger.gz
	SRR9887311_2.fastq.gz	Fastqsanger.gz
	SRR9887312_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 18

Similar Datasets

The transcription factor Bhlhe40 programs mitochondrial regulation of resident CD8+ T cell fitness and functionality

Project description:Tissue-resident memory CD8+ T cells (Trm) share characteristics and core residency gene programs with tumor-infiltrating lymphocytes (TILs). However, the transcriptional, metabolic and epigenetic regulation of Trm cell and TIL differentiation, maintenance and function are largely undefined. Furthermore, it is unknown whether metabolic and epigenetic manipulations can be employed to promote Trm/TIL functional programs for cancer immunotherapy. Here we report a critical mechanism programming the mitochondrial and epigenetic regulation of Trm/TIL functionality in situ. We found that mouse and human Trm/TIL expressed the transcription factor BHLHE40 and the BHLHE40-associated gene signature. Bhlhe40 was specifically required for Trm and TIL development and polyfunctionality. Local PD-1 signaling inhibited TIL Bhlhe40 expression, and Bhlhe40 was critical for TILs reinvigoration following anti-PD therapy. Mechanistically, Bhlhe40 sustained Trm/TIL mitochondrial fitness for the promotion of a functional epigenetic state. Building on these findings, we also identified an epigenetic and metabolic regimen that promoted Trm/TIL gene signatures associated with tissue residency and poly-functionality through in vitro T cell screening. Strikingly, this regimen empowered the anti-tumor activity of CD8+ T cells and possessed therapeutic potential even at an advanced tumor stage in mouse models. Our results provide mechanistic insights on the local regulation of Trm and TIL function, and offer a viable strategy for developing novel immunotherapeutic means for cancer.

2019-09-17 | GSE135278 | GEO

The Transcription Factor Bhlhe40 Programs Mitochondrial Regulation of Resident CD8+ T Cell Fitness and Functionality.

Project description:Tissue-resident memory CD8+ T (Trm) cells share core residency gene programs with tumor-infiltrating lymphocytes (TILs). However, the transcriptional, metabolic, and epigenetic regulation of Trm cell and TIL development and function is largely undefined. Here, we found that the transcription factor Bhlhe40 was specifically required for Trm cell and TIL development and polyfunctionality. Local PD-1 signaling inhibited TIL Bhlhe40 expression, and Bhlhe40 was critical for TIL reinvigoration following anti-PD-L1 blockade. Mechanistically, Bhlhe40 sustained Trm cell and TIL mitochondrial fitness and a functional epigenetic state. Building on these findings, we identified an epigenetic and metabolic regimen that promoted Trm cell and TIL gene signatures associated with tissue residency and polyfunctionality. This regimen empowered the anti-tumor activity of CD8+ T cells and possessed therapeutic potential even at an advanced tumor stage in mouse models. Our results provide mechanistic insights into the local regulation of Trm cell and TIL function.

| S-EPMC6903704 | biostudies-literature

Microarray data for Bhlhe40-sufficient and -deficient resident macrophages

Project description:Most tissue-resident macrophage populations develop during embryogenesis, self-renew in the steady state, and can expand during type 2 immunity. Whether shared mechanisms regulate macrophage proliferation in homeostasis and disease is unclear. We found that the transcription factor Bhlhe40 was cell-intrinsically required in large peritoneal macrophages (LPMs) for self-renewal and maintenance, but was not required in other resident macrophages. Bhlhe40 was selectively necessary in LPMs for proliferation, but not polarization, in response to IL-4. During a helminth infection, Bhlhe40 was required for normal LPM cell cycling. Bhlhe40 repressed the expression of Maf and Mafb and directly promoted expression of cell cycle-related transcripts to enable proliferation of LPMs. Genomic sites bound by Bhlhe40 in LPMs included some co-bound by the macrophage lineage-determining factor PU.1 and others uniquely bound by Bhlhe40, including Maf and cell cycle-related loci. Our findings demonstrate a tissue-specific control mechanism regulating resident macrophage proliferation in homeostasis and type 2 immunity.

2019-04-30 | GSE125727 | GEO

Microarray data for Bhlhe40-sufficient and -deficient resident macrophages

Project description:Microarray data for Bhlhe40-sufficient and -deficient resident macrophages

| PRJNA517406 | ENA

Expression data from mouse differentiated Bhlhe40-GFPneg and Bhlhe40-GFPpos TH17 cells

Project description:Microarray data on TH17 cells from Bhlhe40-GFP reporter mice We used microarrays to detail the global programme of gene expression in polarized Bhlhe40-GFPneg and Bhlhe40-GFPpos TH17 cells Purified naÃ¯ve CD4 T cells from spleen were polarized under TH17 condition in vitro. On day 4, cells were stimulated with PMA and ionomycin, and sorted by their Bhlhe40-GFP expression prior to microarray analysis

2016-01-04 | E-GEOD-75407 | biostudies-arrayexpress

Chromatin immunoprecipitation sequencing (ChIP-Seq) for Bhlhe40 from naïve and IL-4c-stimulated large peritoneal macrophages (LPMs)

2019-04-30 | GSE125729 | GEO

Bhlhe40 and Bhlhe41 transcription factors regulate alveolar macrophage self-renewal and identity

Project description:Tissues in multicellular organisms are ‘serviced’ by resident macrophages, which perform both generic and tissue-specific functions. The latter relies on unique tissue-specific molecular programs induced by signals from the microenvironment and executed through a combinatorial action of tissue-specific and broadly expressed transcriptional regulators. Here, we identify the transcription factors Bhlhe40 and Bhlhe41 as novel regulators of alveolar macrophages (AMs) – a population that provides the first line of immune defense and executes homeostatic functions in lung alveoli. In the absence of these factors, AMs exhibited decreased proliferation that resulted in a severe disadvantage of knockout AMs in a competitive setting. Gene expression analyses revealed a broad cell-intrinsic footprint of Bhlhe40/Bhlhe41-deficiency manifested by a downregulation of AM signature genes and induction of signature genes of other macrophage lineages. Genome-wide characterization of Bhlhe40 DNA binding suggested that these transcription factors directly repress the expression of lineage-inappropriate genes in AMs. Taken together, these results identify Bhlhe40 and Bhlhe41 as key regulators of AM self-renewal and guardians of their identity.

2019-07-30 | GSE135018 | GEO

Expression data from mouse differentiated Bhlhe40-GFPneg and Bhlhe40-GFPpos TH17 cells

2016-01-04 | GSE75407 | GEO

Snai2 and Snai3 transcriptionally regulate cellular fitness and functionality of T cell lineages through distinct gene programs

Project description:T lymphocytes are essential contributors to the adaptive immune system and consist of multiple lineages that serve various effector and regulatory roles. As such, precise control of gene expression is essential to the proper development and function of these cells. Previously, we identified Snai2 and Snai3 as being essential regulators of immune tolerance partly due to the impaired function of CD4+ regulatory T cells in Snai2/3 conditional double knockout mice. Here we extend those previous findings using a bone marrow transplantation model to provide an environmentally unbiased view of the molecular changes imparted onto various T lymphocyte populations once Snai2 and Snai3 are deleted. The data presented here demonstrate that Snai2 and Snai3 transcriptionally regulate the cellular fitness and functionality of not only CD4+ regulatory T cells but effector CD8α+ and CD4+ conventional T cells as well. This is achieved through the modulation of gene sets unique to each cell type and includes transcriptional targets relevant to the survival and function of each T cell lineage. As such, Snai2 and Snai3 are essential regulators of T cell immunobiology.

2016-10-28 | GSE74467 | GEO

STAT4 promotes Bhlhe40 induction to drive protective IFN-g from natural killer cells during viral infection [BHLHE40 CUT&RUN]

Project description:NK cells represent a cellular component of the mammalian innate immune system, and mount rapid responses against viral infection, including the secretion of the potent anti-viral effector cytokine IFN-g. Following mouse cytomegalovirus (MCMV) infection, Bhlhe40 was the most highly induced transcription factor in NK cells among the basic helix-loop-helix family. Bhlhe40 upregulation in NK cells depended upon IL-12 and IL-18 signals, with the promoter of Bhlhe40 enriched for STAT4 and the permissive histone H3K4me3, and STAT4-deficient NK cells showing an impairment of Bhlhe40 induction and diminished H3K4me3. Transcriptomic and protein analysis of Bhlhe40-deficient NK cells revealed a defect in IFN-g production during MCMV infection, resulting in diminished protective immunity following viral challenge. Finally, we provide evidence that Bhlhe40 directly promotes IFN-g by binding throughout the Ifng loci in activated NK cells. Thus, our study reveals how STAT4-mediated control of Bhlhe40 drives protective IFN-g secretion by NK cells during viral infection.

2023-09-13 | GSE242900 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data