Fate mapping via Ms4a3 expression history traces monocyte-derived cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE134523 | GEO | 2019/08/19
REPOSITORIES: GEO
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Project description:Administration of G-CSF mobilizes a unique population of CD11b+Ly6C+CD34+mature monocytes that can inhibit GVHD in murine models of BMT via an iNOS-dependent mechanism. The transcriptional profiles of flow sorted lineage-CD11b+CD34+ cells from G-CSF treated mice were compared with conventional splenic Ly6C+ and Ly6C- monocytes, progenitor cells and cultured myeloid-derived suppressor cells. Further comparisons were made with lineage-CD11b+CD34+ cells from G-CSF treated mice that had been grown in culture or that were derived from iNOS ko mice. We used microarrays to detail the global programme of gene expression underlying diffrenetiation of each of these cell types Lin-CD11b+CD34+ populations were isolated directly from the spleens of G-CSF-treated C57BL/6 mice or iNOS ko mice. In untreated C57BL/6 mice, Lin-CD11b+CD115+Ly6C+ and Lin-CD11b+CD115+Ly6C- monocytes were isolated from the spleen and Lin-CD117+CD115+CD135-Ly6C+CD11b- common monocyte progenitors were isolated from the bone marrow. Myeloid-derived suppressor cells (Ly6C+CD11b+ cells derived from G-CSF, GM-CSF and IL-13 cultured C57BL/6 bone marrow) were also isolated and compared with the above populations. Lin-CD11b+CD34+ spleen cells derived from G-CSF-treated C57BL/6 mice were cultured for 3 days in Flt3 ligand and SCF and then compared to the original input population.
2015-04-01 | E-GEOD-65670 | biostudies-arrayexpress
Project description:Purpose: In our study, we identified a heterogeneity among bone marrow (BM) Ly6Chi monocytes, which can be subdivided the expression of CXCR4. In order to understand the development of BM monocytes, the goal of this experiment is to compare the transcriptome of these 2 BM Ly6Chi monocyte subsets to those of the common monocyte progenitor (cMoP) and Ly6Clo monocytes.
2016-09-29 | GSE86079 | GEO
Project description:We investigated the innate immune system in the SOD1 ALS model. We found that splenic Ly6CHi monocytes were activated and their progressive recruitment to the spinal cord, but not brain, correlated with neuronal loss. We found a decrease in resident microglia in the spinal cord with disease progression. Two months prior to disease onset, splenic Ly6CHi monocytes had an M1 signature which included increased CCR2. At one month prior to disease onset, microglia expressed increased CCL2 and other chemotaxis-associated molecules. Microglia derived from the spinal cord of SOD1 mice recruited Ly6C+ monocytes to the CNS. Treatment with anti-Ly6C mAb modulated the Ly6CHi monocyte cytokine profile, reduced monocyte recruitment to the spinal cord, diminished neuronal loss and extended survival. In humans with ALS, CD14+/CD16- monocytes (analogue of Ly6CHi monocytes) exhibited an ALS specific microRNA inflammatory signature similar to that observed in the SOD1 mouse providing a direct link between the animal model and the human disease. Thus, the SOD1-like profile of monocytes in ALS subjects may serve as a biomarker for disease stage or progression. Our results suggest that recruitment of inflammatory monocytes plays an important role in disease progression and that modulation of these cells is a potential therapeutic approach. This study used the NanoString nCounter hybridization system and nCounter miRNA expression assays to identify and quantitate miRNAs in blood CD14+CD16- monocytes from ALS, MS and HC subjects Total RNA was isolated from FACS sorted CD14+CD16- blood-derived monocytes from sporadic ALS (n=8), MS (n=8) and HC (n=8) subjects. RNA was profiled using the NanoString nCounter miRNA expression assay
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Project description:Monocytes are integral cells of the innate immune system that play important roles in host defence and tissue repair. It is well established that monocytes are derived from the common monocyte progenitor (cMoP) in the bone marrow (BM) before giving rise to Ly6Chi mature monocytes that enter the circulation. However, our lab has discovered that BM Ly6Chi monocytes are not homogenous, and consist of two subpopulations (CXCR4hi and CXCR4lo) in both mice and humans. In particular, the CXCR4hi subset (termed transitional pre-monocyte (TpMo) population) actively proliferates in the BM and matures into the CXCR4lo subset, which represents mature Ly6Chi monocytes. Nevertheless, how this TpMo population may behave beyond their precursor role in the BM remains undefined. While TpMos have been shown to be strictly immobilized in the BM in the steady state, our preliminary data revealed the mobilization of TpMos into the circulation during sepsis. Furthermore, TpMos were found to give rise to more macrophages than mature Ly6Chi monocytes. Our data hence suggests a critical peripheral role for TpMos that may implicate the outcome of sepsis and possible potential implications in future therapies associated with monocytes. Based on our preliminary findings, we aim to have a better understanding of these monocyte subsets and how they are transcriptionally distinct when they have become macrophages. In particular, we would like to determine if TpMo-derived macrophages are less inflammatory compared to mature monocyte-derived macrophages.
2022-03-09 | GSE192449 | GEO
Project description:We investigated the innate immune system in the SOD1 ALS model. We found that splenic Ly6CHi monocytes were activated and their progressive recruitment to the spinal cord, but not brain, correlated with neuronal loss. We found a decrease in resident microglia in the spinal cord with disease progression. Two months prior to disease onset, splenic Ly6CHi monocytes had an M1 signature which included increased CCR2. At one month prior to disease onset, microglia expressed increased CCL2 and other chemotaxis-associated molecules. Microglia derived from the spinal cord of SOD1 mice recruited Ly6C+ monocytes to the CNS. Treatment with anti-Ly6C mAb modulated the Ly6CHi monocyte cytokine profile, reduced monocyte recruitment to the spinal cord, diminished neuronal loss and extended survival. In humans with ALS, CD14+/CD16- monocytes (analogue of Ly6CHi monocytes) exhibited an ALS specific microRNA inflammatory signature similar to that observed in the SOD1 mouse providing a direct link between the animal model and the human disease. Thus, the SOD1-like profile of monocytes in ALS subjects may serve as a biomarker for disease stage or progression. Our results suggest that recruitment of inflammatory monocytes plays an important role in disease progression and that modulation of these cells is a potential therapeutic approach This study used the NanoString nCounter hybridization system and the Nanostring GX Human Immunology and Nanostring Human Inflammation assays to identify and quantitate immune-related genes in blood CD14+CD16- monocytes from ALS, MS and HC subjects Total RNA was isolated from FACS sorted CD14+CD16- blood-derived monocytes from sporadic sALS (n=10), fALS (n=4) and HC (n=10) subjects. RNA was profiled using the Nanostring GX Human Immunology and Nanostring Human Inflammation assays
2012-07-25 | E-GEOD-39642 | biostudies-arrayexpress
Project description:Monocytes comprise two major subsets, Ly6Chi classical monocytes and Ly6Clo non-classical monocytes. Notch2 signaling in Ly6Chi monocytes triggers transition to Ly6Clo monocytes, which require Nr4a1, Bcl6, Irf2 and Cebpb. By comparison, less is known about transcriptional requirements for Ly6Chi monocytes. We find transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα) is highly expressed in Ly6Chi monocytes, but down-regulated in Ly6Clo monocytes. A few previous studies described the requirement of C/EBPα in the development of neutrophils and eosinophils. However, role of C/EBPα for in vivo monocyte development has not been understood. We deleted the Cebpa +37 kb enhancer in mice, eliminating hematopoietic expression of C/EBPα, reproducing the expected neutrophil defect. Surprisingly, we also discovered a severe and selective loss of Ly6Chi monocytes, while preserving Ly6Clo monocytes. We find that BM progenitors from Cebpa +37–/– mice rapidly progress through the cMoP stage to develop directly into Ly6Clo monocytes even in the absence of Notch2 signaling. These results identify a previously unrecognized role for C/EBPα in maintaining Ly6Chi monocyte identity.
2024-03-18 | GSE254202 | GEO
Project description:Currently, it is unclear if all monocyte subsets exhibit osteoclastogenic potential. Furthermore, the role of lineage determining TFs in regulating OC differentiation on a genome-wide scale remains poorly understood. In this study, we utilized a novel Irf8 conditional knockout (Irf8 cKO) mouse model to characterize the importance of IRF8 in OC progenitor development and epigenetic regulation of OC differentiation. To identify global transcriptional program governing the osteoclastogenic potential of Ly6Chi, Ly6Cint, and Ly6C– monocytes, and how it may be further influenced by IRF8 deficiency, we performed RNA-seq on sorted Ly6Chi, Ly6Cint, and Ly6C– cells from WT and Irf8 cKO mice. Cells were analyzed prior to (BMMs) and 4 days after RANKL stimulation (OCs). Here we show that WT Ly6Chi and Ly6Cint monocytes developmentally contain OC-specific transcripts, which are augmented upon RANKL stimulation. Additionally, in the absence of IRF8, OC-specific transcripts in all three monocyte subsets are primed to robustly respond to RANKL stimulation.
2020-09-11 | GSE151480 | GEO
Project description:microRNAs are assumed to fine-tune cellular mRNA expression levels predisposing them for the control of cell development and cell fates. However, despite increasing appreciation of the role of miRNAs in controlling myeloid cell functions and some evidence for their contribution in in vitro monocyte differentiation, the in vivo role of specific miRNAs in the development and homeostasis of myeloid cells remains to be investigated. Here we profiled the microRNA expression of 8 different myeloid cell population including myeloid precursors (MP), myeloid dendritic cell precursors (MDP), common dendritic cell precursors (CDP), plasmacytoid dendritic cells (PDC) and Gr1+ monocytes from the bone marrow and three different spenic denritic cells (DCs): CD4+ DCs, CD8+ DCs and CD4-CD8- DCs. The source of the cells were female C57BL/6 animals in an age of 6 weeks. The FACS isolation was done on a pooled cell suspension from a minimum of 5 animals. C57BL/6 mice in an age of 6 weeks were purchased from Harlan. For bone marrow (BM) precursor isolation, ACK (0.15M NH4Cl, 0.1M KHCO3, 1mM EDTA in PBS) lyzed BM cells from femur and tibia were pooled from 15 mice and enriched by MACS with biotinylated CD135 (A2F10) followed by anti-biotin MACS beads (Miltenyi). The enriched fraction was further stained with Streptavidin-PerCP, CD117 (2B8), CD115 (AFS98) and lineage antibody cocktail (CD11b (M1/70), CD3 (145-2C11), CD4 (GK1.5), CD8M-NM-1 (53-6.7), Gr1 (RB6-8C5), Sca-1 (D7), B220 (RA3-6B2), Ter-119, CD11c (N418), NK1.1 (PK136)). Splenic dendritic cells were pre-enriched from 8 mice by CD11c MACS beads (Miltenyi) and further stained for CD8M-NM-1, CD4, CD11c and CD86 (PO3). BM plasmacytoid DCs were isolated from 5 mice, followed by Ficoll enrichment and stained for CD11c, CD317 (927) and Siglec H (eBio440c). BM monocytes were isolated from Ficoll enriched BM cells from 5 mice. Staining markers were: CD11b, Gr1 and CD115. All antibodies were purchased from BioLegend or eBioscience if not indicated otherwise. A FACSAria cytometer (Becton-Dickinson) was used for sorting and duplets were excluded by their FSC-H vs. FSC-W appearance.
2012-11-22 | E-GEOD-42434 | biostudies-arrayexpress
Project description:Monocytes are circulating myeloid immune precursor cells that are generated in the bone marrow (BM). Upon their release into the circulation, monocytes are recruited to inflammatory sites, where they differentiate into monocyte-derived effector cells. In absence of overt inflammation, monocytes also extravasate into selected tissues, where they complement tissue-resident macrophage compartments. Recent studies have uncovered binary developmental trajectories of monocytes in the BM with Neutrophil-like (NeuMo) and dendritic cell (DC)-like (DCMo) monocytes differentiating downstream of granulocyte-macrophage progenitors (GMP) and macrophage-dendritic cell progenitors (MDP), respectively (Weinreb et al., 2020; Yanez et al., 2017). Yet, the molecular cues that dictate BM monocyte differentiation remain incompletely understood. The COMMD (copper metabolism MURR1 domain) family includes 10 evolutionarily conserved proteins. Functions of COMMD proteins are still being defined, but they seem to play non-redundant roles in regulating transcription and protein trafficking. Utilizing conditional COMMD10 knockout mice we uncovered a role for COMMD10 in limiting inflammasome activation in Ly6Chi monocytes during experimental sepsis and colitis (Mouhadeb et al., 2018), and in supporting phagolysosomal biogenesis and maturation in KCs and BM-derived macrophages infected with Staphylococcus aureus (Ben Shlomo et al., 2019). Hence, these studies mark COMMD10 as a candidate mediator of monocyte and macrophage fate and immune responses. Here we studied the effect of COMMD10-deficiency on Ly6Chi monocyte differentiation. We show that COMMD10-deficiency in steady state Ly6Chi monocytes promotes a differentiation bias towards NeuMo fate.
2021-10-05 | GSE183495 | GEO
Project description:Macrophage colony stimulating factor-1 (CSF-1) plays a critical role in maintaining myeloid lineage cells. However, congenital global deficiency of CSF-1 (Csf1op/op) causes severe musculoskeletal defects that may indirectly affect hematopoiesis. Indeed, we show here that osteolineage-derived Csf1 prevented developmental abnormalities but had no effect on monopoiesis in adulthood. However, ubiquitous deletion of Csf1 conditionally in adulthood decreased monocyte survival, differentiation, and migration, independent of its effects on bone development. Bone histology revealed that monocytes reside near sinusoidal endothelial cells (ECs) and leptin receptor (Lepr)-expressing perivascular mesenchymal stromal cells (MSCs). Targeted deletion of Csf1 from sinusoidal ECs selectively reduced Ly6C- monocytes, whereas combined depletion of Csf1 from ECs and MSCs further decreased Ly6Chi cells. Moreover, EC-derived CSF-1 facilitated recovery of Ly6C- monocytes and protected mice from weight loss following induction of polymicrobial sepsis. Thus, monocytes are supported by distinct cellular sources of CSF-1 within a perivascular BM niche.
2022-05-03 | GSE201162 | GEO