Next Generation Sequencing of transcriptomes to reveal the role of HDAC3 in regulating the development of LMPP and CD115- CDP and bone marrow pDCs
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA809366 | ENA |
REPOSITORIES: ENA
Similar Datasets
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
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
Project description:Genome-wide maps of H3K27ac in HDAC3 knockout bone marrow pDCs compared with control pDCs
| PRJNA809374 | ENA
Project description:Purpose: The goals of this study are to compare CD115- monocytes to CD115+ monocytes from naïve and tumor-bearing mice (EL4) with high-throughput data analysis. Methods: CD115- monocytes and CD115+ monocytes were sorted by flow cytomentry separatly. Total RNA was extracted from cells using the RNeasy Mini Kit (QIAGEN, Hilden, Germany) and residual DNA was removed with a DNA-free Kit (Thermo Fisher Scientific, Waltham, MA, USA) according to the manufacturer’s instructions. Samples were loaded onto a 1% agarose gel before electrophoresis. DNA-free conditions were confirmed by SYBR Gold staining (Invitrogen). The quantity and the quality of RNA was evaluated by Nanodrop 2000 spectrophotometer (Thermo Fisher Scientific) and bioanalyzer (Agilent 2100; Agilent Technologies, Santa Clara, CA, USA). RNA-Seq libraries were prepared with 1 μg of total RNA from two biological replicates of each group using TruSeq Stranded mRNA LT Sample Prep Kit and analyzed by Illumina Sequencer (both from Illumina, San Diego, CA, USA). Results: We found 1,723 differetially expressed genes (DEGs) between CD115- monocytes and CD115+ monocytes (cutoff value was set at 2-fold). DEGs of interest are invoved in granulocyte, transcription factors, mononuclear phagocytes, and angiogenesis. Conclusions: Our study represents the first detailed DEGs analysis of CD115- monocytes and CD115+ monocytes from naïve and tumor-bearing mice. Our results show that CD115- monocytes may have a closer relationship with neutrophils or PMN-MDSCs than the CD115+ monocytes. Also, our overall transcriptomic analysis further suggests that CD115- M-MDSCs and monocytes are separate subsets of monocytic cells.
2022-03-22 | GSE199008 | GEO
Project description:The peritoneal cavity is home to various immune cells. Previous studies have investigated the heterogenous nature of peritoneal myeloid mononuclear cells. However, up to this date, there are no clear criteria to distinguish peritoneal macrophages and dendritic cells (DCs). In the present study, we delineate the subsets of myeloid mononuclear cells in the mouse peritoneal cavity. Considering phenotypical, functional, and ontogenic features, peritoneal myeloid mononuclear cells are divided into 5 subsets: large peritoneal macrophages (LPMs), small peritoneal macrophages (SPMs), DCs, and 2 MHCII+CD11c+CD115+ subpopulations (i.e., MHCII+CD11c+CD115+CD14-CD206- and MHCII+CD11c+CD115+CD14+CD206+). Among them, 2 subsets of competent antigen presenting cells are demonstrated with distinct functional characteristics, one being DCs and the other being MHCII+CD11c+CD115+CD14-CD206- cells. DCs are able to promote fully activated T cells and superior in expanding cytokine producing inflammatory T cells, whereas MHCII+CD11c+CD115+CD14-CD206- cells generate partially activated T cells and possess a greater ability to induce regulatory T cells under TGF-β and retinoic acid conditions. While the development of DCs and MHCII+CD11c+CD115+CD14-CD206- cells are responsive to the treatment of FLT3L and GM-CSF, the numbers of LPMs, SPMs, and MHCII+CD11c+CD115+CD14+CD206+ cells are only influenced by the injection of GM-CSF. In addition, the analysis of transcriptomes reveals that the gene expression profile of MHCII+CD11c+CD115+CD14+CD206+ cells share high similarity with that of SPMs. Collectively, our study identifies 2 distinct subpopulations of MHCII+CD11c+CD115+ cells, (i) MHCII+CD11c+CD115+CD14-CD206- cells closely related to DCs and (ii) MHCII+CD11c+CD115+CD14+CD206+ cells to SPMs.
2019-07-01 | GSE130424 | GEO
Project description:RNA-Seq analysis of CD115- monocytes and CD115+ monocytes from naïve and tumor-bearing mice
| PRJNA817820 | ENA
Project description:We have shown that intravenous injection of HDAC3 floxed mice with adeno-associated virus (AAV) expressing Cre depletes hepatic HDAC3, upregulates lipogenic gene expression, and causes fatty liver. When AAV-Flag-HDAC3 wild-type (WT) is co-injected along with AAV-Cre, the exogenous HDAC3 is expressed at endogenous levels and can completely rescue fatty liver phenotype. Here we profile transcriptome of the rescued WT livers in comparison with HDAC3-depleted (KO) livers. 4-months old C57BL/6 male mice were co-injected with AAV-Cre or AAV-Cre plus AAV-Flag-HDAC3. Mice were fed ad libitum and harvested at 5 pm (ZT10) at 2-weeks post-injection. Liver total RNA was extracted and hybridized to Affymetrix Mouse Gene 1.0ST array.
2013-11-25 | E-GEOD-49386 | biostudies-arrayexpress
Project description:HDAC3 and HDAC8 are members of class I deacetylases involved in several biological mechanisms and represent a highly sought-after therapeutic target for drug development. It is historically challenging to develop selective deacetylase inhibitors due to their conserved catalytic domains. HDAC3 also has deacetylase-independent activity, which cannot be blocked by conventional enzymatic inhibitors. Recent advances in proteolysis-targeting chimeras (PROTACs) provides an opportunity to eliminate the whole protein selectively, abolishing both enzymatic and scaffolding functions. Here, we report a novel HDAC3/8 dual degrader YX968 that induces highly potent, rapid and selective degradation of both HDAC3 and HDAC8 without trigging pan-HDAC inhibitory effects. Unbiased quantitative proteomics experiments further confirmed its high selectivity. This dual-specific degrader specifically ablates cellular pathways attributed to HDAC3 and HDAC8 and exhibits high potency in killing cancer cells. YX968 represents a new probe for dissecting the complex biological functions of HDAC3 and HDAC8.
2023-07-18 | PXD040941 | Pride
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
Project description:The immune system of SPF mice is dominated by naïve phenotype immune cells, especially within the T cell compartment, and resembles that of neonatal humans (Beura et al., 2016; Reese et al., 2016). Sequential infection of SPF-housed laboratory mice with common experimental pathogens, such as MHV, MCMV, Listeria monocytogenes, LCMV, and influenza A virus (Berton et al., 2022; Reese et al., 2016), or cohousing (CoH) SPF mice with pet store mice carrying multiple pathogenic and commensal bacteria, viruses, and/or fungi (Beura et al., 2016) induces immune system alterations and maturations that more closely resemble the adult human immune system. Such microbial exposure drastically alters the composition and function of the immune system of laboratory mice, which can significantly influence the overall outcome (and survival) to subsequent infection. Here we report CD11b+ CD115+ monocytes sorted from female specific pathogen-free (SPF) C57BL/6N (B6) mice co-housed with petstore mice for 60 days are transcriptionally different than SPF CD11b+ CD115+ monocytes
2023-10-26 | GSE237883 | GEO