Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

39 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A negative feedback loop of transcription factors specifies alternative dendritic cell chromatin states (RNA-Seq)

ABSTRACT: During hematopoiesis, cells originating from the same stem cell reservoir differentiate into distinct cell types. The mechanisms enabling common progenitors to differentiate into distinct cell fates are not fully understood. Here, we identify chromatin-regulating and cell-fate-determining transcription factors (TF) governing dendritic cell (DC) development by annotating the enhancer and promoter landscapes of the DC lineage. Combining these analyses with detailed over-expression, knockdown and ChIP-Seq studies, we show that Irf8 functions as a plasmacytoid DC epigenetic and fate-determining TF, regulating massive, cell-specific chromatin changes in thousands of pDC enhancers. Importantly, Irf8 forms a negative feedback loop with Cebpb, a monocyte-derived DC epigenetic fate-determining TF. We show that using this circuit logic, differential activity of TF can stably define epigenetic and transcriptional states, regardless of the microenvironment. More broadly, our study proposes a general paradigm that allows closely related cells with a similar set of signal-dependent factors to generate differential and persistent enhancer landscapes. Here analyzed 2 experiments, each one contains samples of moDC and pDC ex vivo cultured cells. The first experiment contains 32 samples of moDC and pDC following stimulation with various TLR stimulators. The second experiment contains 8 samples of moDC and pDC following perturbations; Cebpb and Irf8 knock down or over expression.

ORGANISM(S): Mus musculus

SUBMITTER: Ido Amit

PROVIDER: E-GEOD-62704 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

A negative feedback loop of transcription factors specifies alternative dendritic cell chromatin states (ChIP-Seq)

Project description:During hematopoiesis, cells originating from the same stem cell reservoir differentiate into distinct cell types. The mechanisms enabling common progenitors to differentiate into distinct cell fates are not fully understood. Here, we identify chromatin-regulating and cell-fate-determining transcription factors (TF) governing dendritic cell (DC) development by annotating the enhancer and promoter landscapes of the DC lineage. Combining these analyses with detailed over-expression, knockdown and ChIP-Seq studies, we show that Irf8 functions as a plasmacytoid DC epigenetic and fate-determining TF, regulating massive, cell-specific chromatin changes in thousands of pDC enhancers. Importantly, Irf8 forms a negative feedback loop with Cebpb, a monocyte-derived DC epigenetic fate-determining TF. We show that using this circuit logic, differential activity of TF can stably define epigenetic and transcriptional states, regardless of the microenvironment. More broadly, our study proposes a general paradigm that allows closely related cells with a similar set of signal-dependent factors to generate differential and persistent enhancer landscapes. Here analyzed 2 experiments, each one contains samples of moDC and pDC ex vivo cultured cells. The first experiment contains 32 samples of moDC and pDC following stimulation with various TLR stimulators. The second experiment contains 8 samples of moDC and pDC following perturbations; Cebpb and Irf8 knock down or over expression.

2014-12-11 | E-GEOD-62702 | biostudies-arrayexpress

A negative feedback loop of transcription factors specifies alternative dendritic cell chromatin states (ATAC-Seq)

Project description:During hematopoiesis, cells originating from the same stem cell reservoir differentiate into distinct cell types. The mechanisms enabling common progenitors to differentiate into distinct cell fates are not fully understood. Here, we identify chromatin-regulating and cell-fate-determining transcription factors (TF) governing dendritic cell (DC) development by annotating the enhancer and promoter landscapes of the DC lineage. Combining these analyses with detailed over-expression, knockdown and ChIP-Seq studies, we show that Irf8 functions as a plasmacytoid DC epigenetic and fate-determining TF, regulating massive, cell-specific chromatin changes in thousands of pDC enhancers. Importantly, Irf8 forms a negative feedback loop with Cebpb, a monocyte-derived DC epigenetic fate-determining TF. We show that using this circuit logic, differential activity of TF can stably define epigenetic and transcriptional states, regardless of the microenvironment. More broadly, our study proposes a general paradigm that allows closely related cells with a similar set of signal-dependent factors to generate differential and persistent enhancer landscapes. Here we profiled accessible chromatin of moDC and pDC using ATAC-seq assay, developed by Buenrostro et al. (2013)

2014-12-14 | E-GEOD-62703 | biostudies-arrayexpress

A negative feedback loop of transcription factors specifies alternative dendritic cell chromatin states (RNA-Seq)

2014-12-14 | GSE62704 | GEO

A negative feedback loop of transcription factors specifies alternative dendritic cell chromatin states (ATAC-Seq)

2014-12-14 | GSE62703 | GEO

A negative feedback loop of transcription factors specifies alternative dendritic cell chromatin states (ChIP-Seq)

2014-12-11 | GSE62702 | GEO

L-Myc expression by dendritic cells is required for optimal T-cell priming

Project description:The transcription factor IRF8 is a critical regulator of plasmacytoid dendritic cell (pDC) and classical dendritic cell (cDC) development in both mouse and man. Yet the downstream molecular targets that regulate DC homeostasis and development are largely unknown. A recent study using gene expression analysis of IRF8-deficient myeloid and lymphoid progenitors identified the Myc paralog Mycl1 as a potential transcriptional target of IRF8. We report here that Mycl1 is a mediator of DC homeostasis at steady state and during inflammation, and its expression is regulated by IRF8 in multiple DC lineages. We have further validated these observations with ChIP-Seq of IRF8 binding to the Mycl1 locus. Notably, IRF8 binding to Mycl1 locus is independent of an interaction with the AP1 factor, BATF3. Additionally, our genome-wide survey of IRF8 binding identified both EICE and AICE motifs. Examination of IRF8 binding in dendritic cells

2013-12-14 | E-GEOD-53311 | biostudies-arrayexpress

A lncRNA identifies Irf8 enhancer element in negative feedback control of dendritic cell differentiation

Project description:Dendritic cells (DC) are professional antigen presenting cells that develop from multipotent progenitors (MPP) and DC committed common DC progenitors (CDP) and further differentiate into different subsets: classical DC type 1 and 2 (cDC1 and cDC2, respectively) and plasmacytoid DC (pDC). In this study MPP, CDP, cDC1, cDC2 and pDC were obtained in a two-step in vitro culture system according to Felker et al., J. Immunol. 185, 5326-5335, 2010. Briefly, mouse bone marrow cells were first amplified with a specific cytokine cocktail and then induced to differentiate into DC with Flt3 ligand. MPP, CDP, cDC1, cDC2 and pDC were obtained by FACS sorting as follows: MPP: Gr1- CD117hi CD135low/-; CDP: Gr1- CD117int CD135+ CD115+; cDC1: CD11c+ CD11blow/- XCR1+; cDC2: CD11c+ CD11b+ XCR1- and pDC: CD11c+ CD11b- B220+. FACS sorted cells were then subjected to Omni-ATAC-seq, nuclear-titrated (NuTi) Capture-C targeting Irf8 promoter, and RNA-seq analysis. ATAC-seq data of cDC1 and pDC are published (Li et al., Genome Biol. 20, 45, 2019; GSE118221). ATAC-seq data of MPP, CDP and cDC2, NuTi Capture-C and RNA-seq data of MPP, CDP, cDC1, cDC2 and pDC are published here. CD11c+ CD11b+ B220- cDC and CD11c+ CD11b- B220+ pDC were obtained by FACS sorting and subjected to ChIP-seq analysis of IRF8 and are published here.

2023-03-01 | GSE198651 | GEO

Optimization of the Irf8 +32 kb enhancer disrupts dendritic cell lineage segregation [scRNA-seq]

Project description:Autoactivation of lineage-determining transcription factors (TFs) mediates bistable expression to generate distinct cell phenotypes essential for complex body plans. Classical dendritic cells type 1 (cDC1) and type 2 (cDC2) provide non-redundant functions required for defense against distinct immune challenges. Interferon Regulatory Factor 8 (IRF8), the cDC1 lineage-determining TF, undergoes autoactivation in cDC1 progenitors to establish cDC1 identity, yet its expression is downregulated during cDC2 differentiation by an unknown mechanism. This study reveals that the Irf8 +32 kb enhancer, responsible for IRF8 autoactivation, has been tuned to possess low-affinity IRF8 binding sites. Incorporation of multiple high-affinity IRF8 binding sites into the Irf8 +32 kb enhancer induces erroneous IRF8 autoactivation in specified cDC2 progenitors, causing their redirection towards cDC1 and a novel hybrid DC subset with mixed lineage phenotypes. These developmental alterations critically impair both cDC1- and cDC2-dependent arms of immunity. Collectively, our findings underscore the significance of enhancer suboptimization in the developmental segregation of classical dendritic cells required for normal immune function.

2024-08-18 | GSE270060 | GEO

L-Myc expression by dendritic cells is required for optimal T-cell priming

2013-12-14 | GSE53311 | GEO

Optimization of the Irf8 +32 kb enhancer disrupts dendritic cell lineage segregation [bulk RNA-seq]

Project description:Autoactivation of lineage-determining transcription factors (TFs) mediates bistable expression to generate distinct cell phenotypes essential for complex body plans. Classical dendritic cells type 1 (cDC1) and type 2 (cDC2) provide non-redundant functions required for defense against distinct immune challenges. Interferon Regulatory Factor 8 (IRF8), the cDC1 lineage-determining TF, undergoes autoactivation in cDC1 progenitors to establish cDC1 identity, yet its expression is downregulated during cDC2 differentiation by an unknown mechanism. This study reveals that the Irf8 +32 kb enhancer, responsible for IRF8 autoactivation, has been tuned to possess low-affinity IRF8 binding sites. Increasing these affinities in vivo induces erroneous IRF8 autoactivation in specified cDC2 progenitors, causing their redirection towards cDC1 and a novel hybrid DC subset with mixed lineage phenotypes. These developmental alterations critically impair both cDC1- and cDC2-dependent arms of immunity. Collectively, our findings underscore the significance of enhancer suboptimization in the developmental segregation of classical dendritic cells required for normal immune function.

2024-02-01 | GSE241341 | 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