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Expression analysis from Runx2-deficient pDCs from mouse

ABSTRACT: Plasmacytoid dendritic cells (pDCs) rapidly produce type I interferon (IFN-I) in response to viruses and are essential for antiviral immune responses. Although related to classical dendritic cells (cDCs) in their development and expression profile, pDCs possess many distinct features. Unlike cDCs, pDCs develop in the bone marrow (BM) and emerge into peripheral lymphoid organs and tissues as fully differentiated cells. We now report that pDCs specifically express Runx2, a Runt family transcription factor that is essential for bone development. Runx2-deficient murine pDCs developed normally in the BM but were greatly reduced in the periphery. The defect was cell-intrinsic and was associated with the retention of mature Ly49Q+ pDCs in the BM. Runx2 was required for the expression of several pDC-enriched genes including chemokine receptors Ccr2 and Ccr5. Mature pDCs expressed high levels of Ccr5 at the surface, and Ccr5-deficient pDCs in a competitive setting were reduced in the periphery relative to the BM. Thus, Runx2 is required for the emergence of mature BM pDCs into the periphery, in a process that is partially dependent on Ccr5. These results establish Runx2 as a lineage-specific regulator of immune system development.

ORGANISM(S): Mus musculus

PROVIDER: GSE49859 | GEO | 2013/09/30

SECONDARY ACCESSION(S): PRJNA215105

REPOSITORIES: GEO

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Expression analysis from Runx2-deficient pDCs from mouse

Project description:Plasmacytoid dendritic cells (pDCs) rapidly produce type I interferon (IFN-I) in response to viruses and are essential for antiviral immune responses. Although related to classical dendritic cells (cDCs) in their development and expression profile, pDCs possess many distinct features. Unlike cDCs, pDCs develop in the bone marrow (BM) and emerge into peripheral lymphoid organs and tissues as fully differentiated cells. We now report that pDCs specifically express Runx2, a Runt family transcription factor that is essential for bone development. Runx2-deficient murine pDCs developed normally in the BM but were greatly reduced in the periphery. The defect was cell-intrinsic and was associated with the retention of mature Ly49Q+ pDCs in the BM. Runx2 was required for the expression of several pDC-enriched genes including chemokine receptors Ccr2 and Ccr5. Mature pDCs expressed high levels of Ccr5 at the surface, and Ccr5-deficient pDCs in a competitive setting were reduced in the periphery relative to the BM. Thus, Runx2 is required for the emergence of mature BM pDCs into the periphery, in a process that is partially dependent on Ccr5. These results establish Runx2 as a lineage-specific regulator of immune system development. Total BM cells were isolated from Runx2-/- and wildtype fetal liver chimeras 2 months post-reconstitution. BM cells were stained with antibodies against surface markers CD11b, CD11c, BST2, and B220. CD11b- BST2+ B220+ pDCs were purified by flow cytometry on a BD FACS Aria. RNA was purified immediately and prepared for microarray analysis using the Ambion WT labeling kit. Expression was analyzed using Affymetrix Mouse Gene 1.0 ST.

2013-09-30 | E-GEOD-49859 | biostudies-arrayexpress

Genome-wide maps of H3K27ac in HDAC3 knockout bone marrow pDCs compared with control pDCs

Project description:Hdac3 is highly expressed in pDCs, and its deficiency led to substantially impaired development of pDCs, but not cDCs in bone marrow (BM) and spleen. Meanwhile,further investigation demonstrated that HDAC3 was required for the differentiation of pDC from progenitors at different differentiation stages in vitro. Cut & Tag analysis of H3K27ac level in HDAC3 deficient bone marrow pDCs compared with control pDCs, showed that H3K27ac level significantly increased on cDC related genes with PU.1 binding sites in HDAC3 knockout pDCs.

2022-05-27 | GSE197212 | GEO

Next Generation Sequencing of transcriptomes to reveal the role of HDAC3 in regulating the development of LMPP and CD115- CDP and bone marrow pDCs

Project description:Hdac3 is highly expressed in pDCs, and its deficiency led to substantially impaired development of pDCs, but not cDCs in bone marrow (BM) and spleen. Meanwhile, the hematopoietic progenitors with DC differentiation potential, including CMP, CLP and CD115+ CDP were significantly decreased. Although the number of HSC and CD115− CDP were increased, their differentiation potential toward pDCs were abolished. Further investigation demonstrated that HDAC3 was required for the differentiation of pDC from progenitors at different differentiation stages.

2022-05-27 | GSE197207 | GEO

RNA sequencing of bone marrow WT and SLAMF9-/- pDCs

Project description:SLAMF9 belongs to the conserved lymphocytic activation molecule family (SLAMF). Unlike other SLAMs, which have been extensively studied, the role of SLAMF9 in the immune system remained mostly unexplored. By generating CRISPR/CAS9 SLAMF9 knockout mice, we analyzed the role of this receptor in plasmacytoid dendritic cells (pDCs), which preferentially express the SLAMF9 transcript and protein. These cells display a unique capacity to produce type I interferon and bridge between innate and adaptive immune response. Analysis of pDCs in SLAMF9-/- mice revealed an increase of immature pDCs in the BM and enhanced accumulation of pDCs in the lymph nodes. In the periphery, SLAMF9 deficiency resulted in lower levels of the transcription factor SPIB, elevation of pDC survival, and attenuated IFNand TNFproduction. To define the role of SLAMF9 during inflammation, pDCs lacking SLAMF9 were followed during induced experimental autoimmune encephalomyelitis (EAE). SLAMF9-/- mice demonstrated attenuated disease and delayed onset, accompanied by a prominent increase of immature pDCs in the LN, with a reduced co-stimulatory potential and enhanced infiltration of pDCs into the central nervous system (CNS). These results suggest the crucial role of SLAMF9 in pDC differentiation, homeostasis and function in the steady state and during EAE.

2019-08-22 | GSE131633 | GEO

A distinct lineage of origin reveals heterogeneity of plasmacytoid dendritic cells III

Project description:Plasmacytoid dendritic cells (pDCs) are an immune subset devoted to the production of high amounts of type 1 interferons in response to viral infections. While conventional dendritic cells (cDCs) originate mostly from a common dendritic cell progenitor (CDP), pDCs have been shown to develop from both CDPs and common lymphoid progenitors (CLP). Here we found that pDCs developed predominantly from IL7R+ lymphoid progenitor cells. Expression of SiglecH and Ly6D defined pDC lineage commitment along the lymphoid branch. Transcriptional characterization of SiglecH+Ly6D+ precursors indicated that pDC development requires high expression of the transcription factor IRF8, while pDC identity relies on TCF4. RNA sequencing of IL7R+ lymphoid and CDP-derived pDCs mirrored the heterogeneity of mature pDCs observed by single-cell analysis. Both mature pDC subsets are able to secrete type 1 interferons, but only myeloid-derived pDCs share with cDCs their ability to process and present antigen.

2018-06-22 | GSE114314 | GEO

A distinct lineage of origin reveals heterogeneity of plasmacytoid dendritic cells II (scRNAseq)

2018-06-22 | GSE114313 | GEO

A distinct lineage of origin reveals heterogeneity of plasmacytoid dendritic cells I

2018-06-22 | GSE114312 | GEO

Repression of arginase 2 expression in dendritic cells by microRNA-155 is critical for promoting T-cell proliferation

Project description:Microarray experiments were performed to compare the gene expression profiles exhibited by immature and activated bone-marrow (BM) derived conventional DCs (BM-cDCs) and plasmacytoid DCs (BM-pDCs) from WT and miR155-/- mice. (time points 0, 4 and 24 hours)

2015-01-09 | E-MTAB-1527 | biostudies-arrayexpress

Gene expression profile comparison of DC subsets

Project description:To evaluate gene expression profiles on different dendritic cell subsets isolated from spleens of mice We used whole genome microarrays to identify genes specific to pDCs and not other DC subsets in the absence of disease pDCs, CD11b+ cDCs, and CD8+ cDCs were FACS-purified from spleens of healthy C57bl/6 mice

2015-12-10 | E-GEOD-75834 | biostudies-arrayexpress

Transcription profiling of human plasmacytoid dentritic cells co-cultured with activated conventional dendritic cells

Project description:Two well-characterized blood dendritic cell populations, conventional (cDC) and plasmacytoid (pDC), exhibit multiple phenotypic, migratory and functional differences that suggest specialized and may be complementary and coordinated functions. To study this possible coordination, cDCs and pDCs from healthy blood donors were sorted and cDCs were stimulated either with LPS or R848 whereas pDCs were CFSE-labelled and maintained in IL3. Then, CFSE labelled-pDCs and stimulated-cDCs were mixed and co-cultured. Following this "conditioning", CFSE-pDCs were sorted again and further analyzed. Conditioned pDCs showed moderate phenotypic maturation and acquired allostimulatory capacity. Microarray and RT-PCR analyses showed the induction of different genes including chemokines and proinflammatory cytokines that were dependent on the stimulation received from the "conditioner" cDC. Additionally, the differential pattern of conditioning was confirmed by protein secretion analyses with the production of specific chemokines and cytokines by conditioned pDCs. Importantly, conditioning of pDCs by activated cDCs required cell-cell contact.

2011-01-20 | E-MEXP-2555 | biostudies-arrayexpress

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