Similar Datasets
Project description:Calcium pyrophosphate dihydrate (CPPD) crystals are formed locally within the joints, leading to pseudogout. Although the mobilization of local granulocytes can be observed in joints where pseudogout has manifested, the mechanism of this activity remains poorly understood. In this study, CPPD crystals were administered to mice, and the dynamics of splenic and peripheral blood myeloid cells were analyzed. As a result, levels of both granulocytes and monocytes were found to increase following CPPD crystal administration in a concentration-dependent manner, with a concomitant decrease in lymphocytes in the peripheral blood. In contrast, the levels of other cells, such as dendritic cell subsets, T-cells, and B-cells, remained unchanged in the spleen, following CPPD crystal administration. Furthermore, an increase in granulocytes/monocyte progenitors (GMPs) and a decrease in megakaryocyte/erythrocyte progenitors (MEPs) were also observed in the bone marrow. In addition, CPPD administration induced production of IL-1β, which acts on hematopoietic stem cells and hematopoietic progenitors and promotes myeloid cell differentiation and expansion. These results suggest that CPPD crystals act as a "danger signal" to induce IL-1β production, resulting in changes in course of hematopoietic progenitor cell differentiation and in increased granulocyte/monocyte levels, and contributing to the development of gout.
| S-EPMC7794855 | biostudies-literature
Project description:Monocyte to macrophage differentiation involves major biochemical and structural changes in non-dividing cells. In order to elucidate the role of gene regulatory changes during this process, we used high-throughput sequencing to analyze the complete transcriptome and epigenome of human monocytes that were isolated by elutriation and differentiated in vitro by addition of MCSF in serum-free medium. We also investigated the effect of loading the macrophages with modified LDL. We found that many mRNAs and miRNAs were significantly up- or downregulated during differentiation. While there was no correlation between gene expression and DNA methylation changes at transcription start sites, we identified a large number of intra- and intergenic regions that rapidly lost DNA methylation, became nucleosome-free and gained histone marks indicative of active enhancers. Loading of macrophages with modified LDL caused gene expression changes, but no chromatin changes. In summary, our results demonstrate that monocyte to macrophage differentiation is associated with rapid, highly targeted epigenetic changes, whereas lipid uptake mainly affects regulatory circuits of soluble factors.
| EGAS00001001595 | EGA
Project description:Complex regulatory mechanisms control continuous maintenance of myeloid progenitors and renewal of differentiated cells. Transcription factors play a important role in these processes. Here we report that the activation the calcineurin-NFAT signaling pathway inhibit the proliferation of myeloid granulocyte-monocyte progenitor (GMP). Myeloid progenitor subtypes possessed different susceptibilities to Ca2+ flux induction and consequently differential engagement of the calcineurin-NFAT pathway. This study show that inhibition of the calcineurin-NFAT pathway enhanced proliferation of GMPs both in vivo and in vitro. The calcineurin-NFAT signaling in GMPs is initiated through Flt3-L. The inhibition of the calcineurin-NFAT pathway altered the expression of the cell cycle regulation genes CDK4, CDK6, and CDKN1A, thus enabling faster cell cycle progression. The extensive use of NFAT inhibitors in the clinic should take into account that, in addition to the immunosuppression role in lymphoid cells, these NFAT inhibitors also affect the maintenance of the myeloid compartment. Microarray technology was used to understand the effects of NFAT inhibitors on C-kit enriched lineage negative cells.
2014-12-31 | GSE47208 | GEO
Project description:To understand the differentiation program in monocyte/macrophage differentiation, we performed ChIP-seq for IRF8 and H3K4me1 together with gene expression profiling during IRF8-induced monocyte differentiation. Both promoter-proximal and -distal binding of IRF8 associated with induction of the genes especially those related to monocytes/macrophages and immunity. DNA motif analysis for cis-regulatory elements of indirect IRF8 target genes predicted KLF4, essential for Ly6C+ monocyte development, to be a downstream transcription factor regulating the indirect target gene expression. Introduction of KLF4 into an Irf8-/- myeloid progenitor cell line induced a subset of IRF8 target genes and partially induced monocyte/macrophage differentiation. Together, this study revealed the genome-wide behavior of IRF8 and the IRF8-KLF4 axis during monocyte differentiation. Gene expressions in monocyte-like cells differentiated by IRF8 or KLF4 were measured at day 4 after retroviral transductions to myeloid progenitor cell line, Tot2. Two independent experiments were performed.
2013-01-24 | E-GEOD-38810 | biostudies-arrayexpress
Project description:Granulocyte-monocyte progenitors (GMPs) and monocyte-dendritic cell progenitors (MDPs) produce monocytes during homeostasis and in response to increased demand during infection. Both progenitor populations are thought to derive from common myeloid progenitors (CMPs), and a hierarchical relationship (CMP-GMP-MDP-monocyte) is presumed to underlie monocyte differentiation. Here, however, we demonstrate that mouse MDPs arose from CMPs independently of GMPs, and that GMPs and MDPs produced monocytes via similar but distinct monocyte-committed progenitors. GMPs and MDPs yielded classical (Ly6Chi) monocytes with gene expression signatures that were defined by their origins and impacted their function. GMPs produced a subset of "neutrophil-like" monocytes, whereas MDPs gave rise to a subset of monocytes that yielded monocyte-derived dendritic cells. GMPs and MDPs were also independently mobilized to produce specific combinations of myeloid cell types following the injection of microbial components. Thus, the balance of GMP and MDP differentiation shapes the myeloid cell repertoire during homeostasis and following infection.
| S-EPMC5726802 | biostudies-literature
Project description:BACKGROUND:Neonate immune cell functions lack full protection against pathogens. This could be either defect or protective mechanism against overshooting proinflammatory immune responses. We here analysed the function of classical, pro- and anti-inflammatory monocytes and granulocytes from neonates in comparison with adults to investigate if suppressed functions of subpopulations are causative for the unique neonatal immune status. Therefore, reactive oxygen species (ROS) and surface activation markers were quantified in subpopulations. METHODS:In a prospective, longitudinal study granulocyte and monocyte subpopulations were analysed in healthy term infants (>?37?week; n =?13) in comparison with healthy young adults (n =?11). Percentage (%) of cells expressing surface marker (HLA-DR, CD11b, CD62L, CD32, Toll-Like-Receptor-2) and expression per cell, determined by mean fluorescence intensity (MFI), were measured by flow cytometry. ROS production was induced by fMLP, PMA and E. coli in term neonates (>?37?week; n =?13). RESULTS:Classical granulocytes were down- and proinflammatory granulocytes upregulated in neonates compared with adults. Percentage of TLR-2 expressing granulocytes was increased in neonates. Granulocytic ROS production depended on stimulation. The percentage of anti-inflammatory monocytes was increased, while classical monocytes were reduced in neonates. HLA-DR (%, MFI) showed reduction for all monocyte subpopulations, while CD32, CD11b, CD62L and TLR-2 were differently regulated in comparison with adults. CONCLUSIONS:Differentially regulated granulocyte and monocyte subpopulations indicate a unique state of neonatal immunity to fight infections and prevent dysregulation. Further studies are needed to investigate the role of reduced granulocytic ROS formation and reduced monocytic HLA-DR in active disease.
| S-EPMC6884604 | biostudies-literature
Project description:Collombet2016 - Lymphoid and myeloid cell
specification and transdifferentiation
This model is described in the article:
Logical modeling of lymphoid
and myeloid cell specification and transdifferentiation
Samuel Collombet, Chris van Oevelen,
Jose Luis Sardina Ortega, Wassim Abou-Jaoudé, Bruno Di
Stefano, Morgane Thomas-Chollier, Thomas Graf, and Denis
Thieffry
Proceedings of the National Academy of
Sciences of the United States of America
Abstract:
Blood cells are derived from a common set of hematopoietic
stem cells, which differentiate into more specific progenitors
of the myeloid and lymphoid lineages, ultimately leading to
differentiated cells. This developmental process is controlled
by a complex regulatory network involving cytokines and their
receptors, transcription factors, and chromatin remodelers.
Using public data and data from our own molecular genetic
experiments (quantitative PCR, Western blot, EMSA) or
genome-wide assays (RNA-sequencing, ChIP-sequencing), we have
assembled a comprehensive regulatory network encompassing the
main transcription factors and signaling components involved in
myeloid and lymphoid development. Focusing on B-cell and
macrophage development, we defined a qualitative dynamical
model recapitulating cytokine-induced differentiation of common
progenitors, the effect of various reported gene knockdowns,
and the reprogramming of pre-B cells into macrophages induced
by the ectopic expression of specific transcription factors.
The resulting network model can be used as a template for the
integration of new hematopoietic differentiation and
transdifferentiation data to foster our understanding of
lymphoid/myeloid cell-fate decisions.
This model is hosted on
BioModels Database
and identified by:
MODEL1610240000.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2017-06-08 | MODEL1610240000 | BioModels
Project description:The CCAAT/enhancer-binding-protein beta (C/EBPβ) induces primary v-Abl immortalized mouse B cell transdifferentiation (BT) into granulocyte-macrophage-progenitor-like cells (GMPBT). GMPBT maintain cytokine independent self-renewal, lineage choice, and multi-lineage differentiation. Single cell transcriptomics now shows that GMPBT comprise a continuum of myelomonopoietic differentiation states that seamlessly fit into state-to-fate maps of normal GMP. Inactivation of the v-Abl kinase unveiled dependence on activated CSF2-Jak2-Stat5 signaling. Deletion of IRF8 diminished monopoiesis and enhanced granulopoiesis while removal of C/EBPβ abrogated self-renewal and granulopoiesis yet permitted macrophage differentiation. The GMPBT cell culture system is easily scalable to explore the basics of GMP biology and lineage commitment and largely reduces ethically and legislatively arguable, labor-intensive, and costly animal experiments.
2023-11-24 | GSE248415 | GEO
Project description:A recurrent chromosomal translocation detected in cannibalistic acute myeloid leukemia leads to the production of a ZMYND11-MBTD1 fusion protein.
- The ZMYND11-MBTD1 fusion protein is stably incorporated into the endogenous NuA4/TIP60 complex
- ZMYND11-MBTD1 leads to mistargeting of NuA4-TIP60 activity to the coding region of ZMYND11-target genes, altering gene expression and transcript isoforms.
- ZMYND11-MBTD1 binds the MYC gene leading to its upregulation, favoring growth and pluripotency while inhibiting differentiation markers.
2021-04-17 | MSV000087226 | MassIVE
Project description:To understand the differentiation program in monocyte/macrophage differentiation, we performed ChIP-seq for IRF8 and H3K4me1 together with gene expression profiling during IRF8-induced monocyte differentiation. Both promoter-proximal and -distal binding of IRF8 associated with induction of the genes especially those related to monocytes/macrophages and immunity. DNA motif analysis for cis-regulatory elements of indirect IRF8 target genes predicted KLF4, essential for Ly6C+ monocyte development, to be a downstream transcription factor regulating the indirect target gene expression. Introduction of KLF4 into an Irf8-/- myeloid progenitor cell line induced a subset of IRF8 target genes and partially induced monocyte/macrophage differentiation. Together, this study revealed the genome-wide behavior of IRF8 and the IRF8-KLF4 axis during monocyte differentiation.
2013-01-24 | GSE38810 | GEO