Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The histone demethylase KDM5C regulates IRF transcriptional programming impacting dendritic cell population heterogeneity and function (RNA-seq)

ABSTRACT: Functional and phenotypic heterogeneity of dendritic cells (DCs) plays a crucial role in facilitating the development of diverse immune responses essential for host protection. We found that KDM5C, a histone lysine demethylase, regulates conventional DC (cDC) and plasmacytoid DC (pDC) population heterogeneity and function. Mice deficient in KDM5C in DCs, have increased proportions of cDC2Bs and cDC1s, which was partly dependent on type I interferon and pDCs. Loss of KDM5C resulted in an increase in Ly6C- pDCs, which, compared to Ly6C+ pDCs, have limited ability to produce type I interferon and can more efficiently stimulate antigen-specific CD8 T cells. KDM5C-deficient DCs have increased expression of inflammatory genes, altered expression of lineage-specific genes, and reduced function. In response to Listeria infection, KDM5C-deficient mice mounted reduced CD8 responses due to decreased antigen presentation by cDC1s. Thus, KDM5C is a key regulator of DC heterogeneity and a critical driver functional properties of DCs.

ORGANISM(S): Mus musculus

PROVIDER: GSE262866 | GEO | 2024/09/25

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The histone demethylase KDM5C regulates IRF transcriptional programming impacting dendritic cell population heterogeneity and function (CUT&RUN)

Project description:Functional and phenotypic heterogeneity of dendritic cells (DCs) plays a crucial role in facilitating the development of diverse immune responses essential for host protection. We found that KDM5C, a histone lysine demethylase, regulates conventional DC (cDC) and plasmacytoid DC (pDC) population heterogeneity and function. Mice deficient in KDM5C in DCs, have increased proportions of cDC2Bs and cDC1s, which was partly dependent on type I interferon and pDCs. Loss of KDM5C resulted in an increase in Ly6C- pDCs, which, compared to Ly6C+ pDCs, have limited ability to produce type I interferon and can more efficiently stimulate antigen-specific CD8 T cells. KDM5C-deficient DCs have increased expression of inflammatory genes, altered expression of lineage-specific genes, and reduced function. In response to Listeria infection, KDM5C-deficient mice mounted reduced CD8 responses due to decreased antigen presentation by cDC1s. Thus, KDM5C is a key regulator of DC heterogeneity and a critical driver functional properties of DCs.

2024-09-25 | GSE263076 | GEO

Clonal lineage tracing reveals shared origin of conventional and plasmacytoid dendritic cells

Project description:Developmental origins of dendritic cells (DCs) including conventional DCs (cDCs, comprising cDC1 and cDC2 subsets) and plasmacytoid DCs (pDCs) remain unclear. We studied DC development in unmanipulated adult mice using inducible lineage tracing combined with clonal DNA "barcoding" and single-cell transcriptome and phenotype analysis (CITE-Seq). Inducible tracing of Cx3cr1+ hematopoietic progenitors in the bone marrow showed that they simultaneously produce all DC subsets including pDCs, cDC1s and cDC2s. Clonal tracing of hematopoietic stem cells (HSCs) and of Cx3cr1+ progenitors revealed clone sharing between cDC1s and pDCs, but not between the two cDC subsets or between pDCs and B cells. Accordingly, CITE-Seq analyses of differentiating HSCs and Cx3cr1+ progenitors identified progressive stages of pDC development including Cx3cr1+ Ly-6D+ propDCs that were distinct from lymphoid progenitors. These results reveal the shared origin of pDCs and cDCs, and suggest a revised scheme of DC development whereby pDCs share clonal relationship with cDC1s

2022-02-16 | GSE193733 | GEO

DC-SCRIPT (Zpf366) binding in cDC1 and cDC2 cells from wildtype and DC-SCRIPT knockout mice

Project description:The functional diversification of dendritic cells (DCs) is a key step in establishing protective immune responses. Despite the importance of this lineage diversity, its genetic basis is not fully understood. DC-SCRIPT (Zfp366) is a poorly known transcription factor expressed in conventional DCs (cDCs) and their committed bone marrow progenitors but not in plasmacytoid DCs (pDCs). We show that mice lacking DC-SCRIPT displayed substantially impaired development of IRF8-dependent conventional DC1 (cDC1), while cDC2 differentiated normally. The residual DC-SCRIPT-deficient cDC1s had impaired CD8+ T-cell cross-priming, which could be in part explained by the direct control of DC-SCRIPT on IL-12p40 production. Genome-wide mapping of DC-SCRIPT binding and gene expression analyses revealed a key role for DC-SCRIPT in maintaining cDC1 identity via the direct regulation of cDC1 signature genes, including Irf8. Our study reveals DC-SCRIPT to be a critical component of the gene regulatory program shaping the functional attributes of cDC1s.

2021-02-24 | GSE165138 | GEO

RNA-seq analysis of mouse cDC1 and cDC2 populations upon DC-SCRIPT depletion

2021-02-24 | GSE165125 | GEO

RNA-seq and CUT&Tag analysis of mouse cDC1 and cDC2 populations upon DC-SCRIPT depletion

2021-02-24 | GSE165361 | GEO

RNA-seq profiling of wild type and Trim33-/- splenic dendritic cells

Project description:The homeostatic control mechanism of dendritic cells (DCs), including pDCs, cDC1s and cDC2s, is not fully elucidated. Transcriptome profiling of wildtype and TRIM33 conditional knockout mice revealed a key role of TRIM33 in maintaining the homeostasis of all DC subsets.

2024-06-01 | GSE193183 | GEO

IRF8 transcription factor controls survival and function of terminally differentiated conventional and plasmacytoid dendritic cells respectively

Project description:Interferon regulatory factor-8 (IRF8) has been proposed to be essential for development of monocytes, plasmacytoid dendritic cells (pDCs) and type 1 conventional dendritic cells (cDC1s) and remains highly expressed in differentiated DCs. Transcription factors that are required to maintain the identity of terminally differentiated cells are designated “terminal selectors”. Using BM chimeras, conditional Irf8fl/fl mice and various promotors to target Cre recombinase to different stages of monocyte and DC development, we have identified IRF8 as a terminal selector of the cDC1 lineage controlling survival. In monocytes, IRF8 was necessary during early but not late development. Complete or late deletion of IRF8 had no effect on pDC development or survival but altered their phenotype and gene expression profile leading to increased T cell stimulatory function but decreased type 1 interferon production. Thus, IRF8 differentially controls the survival and function of terminally differentiated monocytes, cDC1s and pDCs.

2016-09-20 | GSE85520 | GEO

The transcription factor Zeb2 regulates development of conventional and plasmacytoid DCs by repressing Id2

Project description:Plasmacytoid dendritic cells (pDCs) develop from pre-pDCs, while two lineages of conventional DCs (cDC1s and cDC2s) develop from lineage-committed pre-cDCs. A number of transcription factors (TFs) have been implicated in regulating the development of pDCs (E2-2, Id2) and cDC1s (IRF8, Id2 and Batf3) however, those required for the early commitment of pre-cDCs towards the cDC2 lineage are unknown. Here we identified the TF Zinc finger E box binding homeobox 2 (Zeb2), to play a crucial role in regulating DC development. Zeb2 was expressed from the pre-pDC and pre-cDC stage onwards, and highly expressed in mature pDCs and cDC2s. Mice conditionally lacking Zeb2 in CD11c+ cells had a cell intrinsic reduction in pDCs and cDC2s, coupled with an increase in cDC1s. Conversely, mice in which CD11c+ cells overexpressed Zeb2 displayed a reduction in cDC1s. This was accompanied by altered expression of Id2, which was upregulated in cDC2s and pDCs from conditional knock-out mice. Zeb2 ChIP analysis revealed Id2 to be a direct target of Zeb2. Thus, we conclude that Zeb2 regulates commitment to both the cDC2 and pDC lineages through repression of Id2.

2016-05-01 | GSE79903 | GEO

Plasmacytoid dendritic cell heterogeneity is defined by CXCL10 expression following TLR7 stimulation

Project description:Plasmacytoid dendritic cells (pDCs) play a critical role in bridging the innate and adaptive immune systems. pDCs are specialized type I interferon (IFN) producers, which has implicated them as initiators of autoimmune pathogenesis. However, little is known about the down-stream effectors of type I IFN signaling that amplify autoimmune responses. Here we have used a chemokine reporter mouse to determine the CXCR3 ligand responses in DCs subsets. Following TLR7 stimulation conventional type 1 and type 2 DCs (cDC1 and cDC2 respectively) uniformly upregulate CXCL10. By contrast, the proportion of chemokine positive pDCs was significantly less, and stable CXCL10+ and CXCL10 - populations could be distinguished. CXCL9 expression was induced in all cDC1s, in half of the cDC2 but not by pDCs. In all DC subsets, type I IFNs were the main inducer of CXCR3 chemokines, as IFNAR receptor blocking or deficiency completely abrogated reporter expression. Chemoki ne producing potential was not concordant with the previously identified markers of pDC heterogeneity. Finally, we show that CXCL10+ and CXCL10 - populations are transcriptionally distinct, expressing unique transcriptional regulators, IFN signaling molecules, chemokines, cytokines and cell surface markers. This work highlights CXCL10 as a downstream effector of type I IFN signaling and suggests a division of labor in pDCs subtypes that likely impacts their function as effectors of viral responses and as drivers of inflammation.

2018-06-24 | GSE113770 | GEO

Genome-wide screening identifies Trim33 as an essential regulator of dendritic cell differentiation [Hoxb8-FL Brie sgRNA-Seq]

Project description:The development of all dendritic cells (DCs) including antigen-presenting conventional DCs (cDCs) and cytokine-producing plasmacytoid DCs (pDCs) is controlled by the growth factor Flt3 ligand (Flt3L) and its receptor Flt3. We genetically dissected this common Flt3L-driven pathway of DCs differentiation using CRISPR/Cas9-based dropout screening in a Flt3L-dependent progenitor cell line. Genome-wide screening identified multiple regulators of DC differentiation including the glycosylphosphatidylinositol transamidase complex and arginine methyltransferase Carm1, whose role was confirmed in vivo. It also showed that negative regulators of mTOR signaling, including the subunits of TSC and GATOR1 complexes, restricted progenitor growth but enabled DC differentiation, demonstrating that a TSC- and GATOR1-mediated shutdown of mTOR is required for the process. An orthogonal screen focused on transcriptional regulators showed that Trim33 (TIF-1g) is required for DC differentiation. Conditional targeting in vivo revealed an essential role of Trim33 in the development of all DCs, but not of monocytes or granulocytes. In particular, inducible deletion of Trim33 caused a rapid loss of all DC progenitors, pDCs and the cross-presenting cDC1 subset. The loss of Trim33 from DC progenitors caused spontaneous interferon and inflammatory response, aberrant induction of macrophage-specific genes, and failure to induce DC differentiation program. Collectively, these data elucidate common mechanisms that control Flt3L-driven differentiation of the entire DC lineage, and identify Trim33 as its essential regulator.

2024-04-12 | GSE202942 | 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