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Zeb2 regulates commitment to plasmacytoid dendritic cell and monocyte fate

ABSTRACT: Zeb2 regulates commitment to plasmacytoid dendritic cell and monocyte fate

PROVIDER: PRJNA348101 | ENA |

REPOSITORIES: ENA

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Zeb2 regulates commitment to plasmacytoid dendritic cell and monocyte fate (part 1)

Project description:Recent studies have identified Zeb2 as a transcription factor important for the final maturation of natural killer cells and effector CD8+ T cells. We show that Zeb2 is required for the development of two myeloid cell types, the monocyte and the plasmacytoid dendritic cell, and clarify that this factor is not required for the development of classical dendritic cells.

2016-11-01 | GSE87882 | GEO

Zeb2 regulates commitment to plasmacytoid dendritic cell and monocyte fate (part 2)

2016-11-01 | GSE87883 | GEO

Transcription factor Zeb2 regulates commitment to plasmacytoid dendritic cell and monocyte fate.

Project description:Dendritic cells (DCs) and monocytes develop from a series of bone-marrow-resident progenitors in which lineage potential is regulated by distinct transcription factors. Zeb2 is an E-box-binding protein associated with epithelial-mesenchymal transition and is widely expressed among hematopoietic lineages. Previously, we observed that Zeb2 expression is differentially regulated in progenitors committed to classical DC (cDC) subsets in vivo. Using systems for inducible gene deletion, we uncover a requirement for Zeb2 in the development of Ly-6Chi monocytes but not neutrophils, and we show a corresponding requirement for Zeb2 in expression of the M-CSF receptor in the bone marrow. In addition, we confirm a requirement for Zeb2 in development of plasmacytoid DCs but find that Zeb2 is not required for cDC2 development. Instead, Zeb2 may act to repress cDC1 progenitor specification in the context of inflammatory signals.

| S-EPMC5187668 | biostudies-literature

Zeb2 regulates commitment to plasmacytoid dendritic cell and monocyte fate

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

2016-11-01 | GSE87884 | 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

Comparison of human plasmacytoid dendritic cells and monocyte-derived dendritic cells

Project description:Comparison of human plasmacytoid dendritic cells and monocyte-derived dendritic cells

| PRJEB66498 | ENA

Mus musculus

Project description:Zeb2 regulates commitment to plasmacytoid dendritic cell and monocyte fate (part 2)

| PRJNA348103 | ENA

Mus musculus

Project description:Zeb2 regulates commitment to plasmacytoid dendritic cell and monocyte fate (part 1)

| PRJNA348104 | ENA

Continuous expression of the transcription factor E2-2 maintains the cell fate of mature plasmacytoid dendritic cells

Project description:This SuperSeries is composed of the following subset Series: GSE24726: Gene expression profile of mature plasmacytoid dendritic cells (PDC) after the deletion of transcription factor E2-2 GSE24740: Binding targets of transcription factor E2-2 in human plasmacytoid dendritic cells Refer to individual Series

2010-12-21 | E-GEOD-24785 | biostudies-arrayexpress

ETV3 and ETV6 enable monocyte differentiation into dendritic cells by repressing macrophage fate commitment.

Project description:In inflamed tissues, monocytes differentiate into macrophages (mo-Macs) or dendritic cells (mo-DCs). In chronic nonresolving inflammation, mo-DCs are major drivers of pathogenic events. Manipulating monocyte differentiation would therefore be an attractive therapeutic strategy. However, how the balance of mo-DC versus mo-Mac fate commitment is regulated is not clear. In the present study, we show that the transcriptional repressors ETV3 and ETV6 control human monocyte differentiation into mo-DCs. ETV3 and ETV6 inhibit interferon (IFN)-stimulated genes; however, their action on monocyte differentiation is independent of IFN signaling. Instead, we find that ETV3 and ETV6 directly repress mo-Mac development by controlling MAFB expression. Mice deficient for Etv6 in monocytes have spontaneous expression of IFN-stimulated genes, confirming that Etv6 regulates IFN responses in vivo. Furthermore, these mice have impaired mo-DC differentiation during inflammation and reduced pathology in an experimental autoimmune encephalomyelitis model. These findings provide information about the molecular control of monocyte fate decision and identify ETV6 as a therapeutic target to redirect monocyte differentiation in inflammatory disorders.

| S-EPMC9810530 | biostudies-literature

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