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
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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: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.
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