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Plasmacytoid dendritic cell precursors give rise to conventional dendritic cells via a Siglec-H+ Zbtb46+ Ly6D+ intermediary stage

ABSTRACT: Plasmacytoid dendritic cell precursors give rise to conventional dendritic cells via a Siglec-H+ Zbtb46+ Ly6D+ intermediary stage

PROVIDER: PRJNA784517 | ENA |

REPOSITORIES: ENA

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Plasmacytoid dendritic cell precursors give rise to conventional dendritic cells via a Siglec-H+ Zbtb46+ Ly6D+ intermediary stage

Project description:Plasmacytoid and conventional dendritic cells (pDC, and cDC) are generated from distinct lymphoid and myeloid progenitor cells in murine bone marrow. Despite the early separation of pDC and cDC lineages, CD11c+ MHCII-/lo Siglec-H+ CCR9lo pDC-like precursor cells are able to differentiate into both pDC and cDC. Single-cell transcriptomics and high-dimensional flow cytometry combined with cell fate analysis revealed the heterogeneity and commitment of subsets in this compartment. While Ly6D– cells within this fraction were cDC-committed and B220hi Ly6Dhi Zbtb46– cells were immediate precursors of pDCs, B220lo Ly6Dhi Zbtb46– cells still had the potential to generate cDCs in addition to pDCs. Transition to cDCs occurred via an intermediary stage marked by coexpression of Siglec-H, Ly6D and Zbtb46. Type I IFN stimulation limited cDC and promoted pDC output from these precursors, demonstrating their plasticity in response to inflammation. Thus, flexibility to divert to cDCs is retained in the pDC lineage at later differentiation stages.

2021-12-01 | GSE189780 | GEO

Ly6D+ Siglec-H+ precursors contribute to conventional dendritic cells via a Zbtb46+ Ly6D+ intermediary stage

Project description:Ly6D+ Siglec-H+ precursors contribute to conventional dendritic cells via a Zbtb46+ Ly6D+ intermediary stage

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scRNA-seq of index-sorted myeloid and lymphoid progenitor cells and differentiated pDCs

Project description:Nine different cell types (common dendritic progenitor (CDP), pre-conventional dendritic cell (pre-cDC), common dendritic progenitor (CDPr, according to Rodrigues et al., but this population was flawed in sorting purity), Flt3+ CD11c+ Siglec-H+ CCR9-low B220-low progenitor cell (lo-lo), Flt3 + CD11c+ Siglec-H+ CCR9-low B220-high progenitor cell (lo-hi), plasmacytoid dendritic cell (pDC), Ly6D+ lymphoid progenitor (SP), Ly6D+ Siglec-H+ lymphoid progenitor (DP) and common lymphoid progenitor (CLP)) were sorted to allow for analysis of their transcriptomic relation and/or similarity. The pDC_precursor_scvelo.h5ad file is a processed file ready for direct downstream analysis with scvelo.

2022-05-21 | E-MTAB-11752 | biostudies-arrayexpress

Siglec receptors modulate dendritic cell activation and antigen presentation to T cells in cancer

Project description:Sialoglycan - Siglec axis has been reported to modulate the functions of multiple immune cell types. We found that inhibitory molecules human Siglec-9 and mouse Siglec-E both expressed at high level in tumor-infiltrating dendritic cells(DCs). Therefore, we generated mouse DC cell line lacking the expression of Siglec-E, and used bulk RNA sequencying to analyse how Siglec-E affects DC functions.

2022-03-23 | GSE190700 | GEO

Transcriptome comparison between Zbtb46-deficient and -sufficient group 3 innate lymphoid cells

Project description:We unexpectedly identify one unique subset of group 3 innate lymphoid cells (ILC3s) that co-expresses Zbtb46, a transcription factor that specifies conventional dendritic cells (cDCs). Zbtb46 is robustly expressed by CCR6+ lymphoid tissue inducer (LTi)-like ILC3s that are developmentally and phenotypically distinct from cDCs. To determine the function of Zbtb46 in ILC3s, we performed RNA sequencing on CCR6+ ILC3s sorted from the large intestine of Zbtb46 f/f and Rorc Cre Zbtb46 f/f mice at steady state.

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Zbtb46 coordinates tumor angiogenesis and tumor immunity to control tumor outcome

Project description:Tumor-angiogenesis and -immunity play critical roles in cancer progression and outcome. The existence of an inverse correlation hints at common regulatory mechanism(s) controlling these two processes. Here, we report that Zbtb46, a repressive transcription factor and widely accepted marker for classical dendritic cells (DCs), constitutes one such regulatory mechanism in the tumor microenvironment (TME) and is downregulated in both DCs and endothelial cells (ECs) by tumor-derived factors to facilitate robust tumor growth. This downregulation leads to the development of hallmark features of a pro-tumor environment, including dysfunctional vasculature and immunosuppressive cell accumulation. Analysis of cancer patient data revealed a similar association of a low ZBTB46 expression with an immunosuppressive TME and a worse prognosis. In contrast, upon enforced Zbtb46 expression, the hallmark TME features are mitigated, and tumor growth is restricted. Mechanistically, Zbtb46-deficient ECs were highly angiogenic, and Zbtb46-deficient bone-marrow precursors upregulated Cebpb and showed enhanced myeloid lineage output. Conversely, Zbtb46-maintenance normalizes ECs and, by suppressing Cebpb, skews the polarization of bone-marrow precursors towards more DCs and fewer macrophages, leading to an immune-hot TME. Remarkably, Zbtb46 mRNA treatment synergized with anti-PD1 immunotherapy to improve tumor management in pre-clinical models. These findings identify Zbtb46 as a common regulatory mechanism for angiogenesis and for non-hematopoietic-stem-cell-mediated myeloid lineage skewing in cancer and suggest that maintaining its expression could have therapeutic benefits.

2024-02-24 | GSE226087 | GEO

Gene expression profiles of splenic pDCs in C57Bl6/J and Siglec-H deficient mice

Project description:The steady-state gene expression of pDCs of two different mouse strains was analyzed. Splenic plasmacytoid dendritic cells (pDCs) of Siglec-H knock-out mice on C57Bl& background and the Siglec-H expression littermates (+/+) were enriched and sorted by FACS before generating RNA, followed by cDNA generation and sequencing.

2021-09-15 | GSE179840 | GEO

Zbtb46 expression distinguishes classical dendritic cells and their committed progenitors from other immune lineages

Project description:This SuperSeries is composed of the following subset Series: GSE37028: Microarray analysis of Zbtb46 KO CD4+ Splenic DCs and bone marrow erythroid progenitors GSE37029: Microarray analysis of WT bone marrow myeloid progenitors, BM cultured with GM-CSF and M-CSF, and monocytes treated with GM-CSF Refer to individual Series

2012-05-20 | E-GEOD-37030 | biostudies-arrayexpress

Microarray analysis of Zbtb46 KO CD4+ splenic DCs and bone marrow erythroid progenitors

Project description:Zbtb46 represses G-CSFR and LifR in cDCs Zbtb46 does not significantly affect gene expression in erythroid progenitors

2012-05-21 | GSE37028 | GEO

Type-I interferon inducible genes 26 weeks after mCMV infection in Siglec-H wt and Siglec-H ko mice and their non infected controls

Project description:Type I interferons are critical anti-viral cytokines during virus infections and have also been implicated in the pathogenesis of systemic lupus erythematosus (SLE). The secretion of type I interferon of pDCs is modulated by Siglec-H, a DAP12 associated receptor on pDCs. We showed that Siglec-H deficient pDCs produce more of the type I interferon IFN-Î± in vitro and that Siglec-H ko mice produce more IFN-Î± after murine cytomegalovirus (mCMV) infection in vivo, leading to efficient clearance of the virus. Furthermore, ageing Siglec-H ko mice showed a mild form of systemic autoimmunity. In contrast, Siglec-H ko mice developed a severe form of systemic lupus-like autoimmune disease with strong kidney nephritis several weeks after a single mCMV infection. This induction of systemic autoimmune disease after virus infection in Siglec-H ko mice was accompanied by a type I interferon signature and fully dependent on type I interferon signaling. These results show that Siglec-H normally serves as modulator of type I interferon responses after infection with a persistent virus and thereby prevents induction of autoimmune disease. For microarray experiments gene expression profiles of total splenic cells from two wt and Siglec-H ko mice 26 weeks after infection with luciferase expressing murine Cytomegalovirus (5x105 pfu) or from two uninfected wt and Siglec-H ko control mice were analyzed

2016-03-16 | E-GEOD-79248 | biostudies-arrayexpress

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