Identification of a human clonogenic progenitor with strict monocyte differentiation potential - a counterpart of mouse cMoPs
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE98090 | GEO | 2017/04/24
SECONDARY ACCESSION(S): PRJNA383983
REPOSITORIES: GEO
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Project description:We sought to determine the impact of chorioamnionitis exposure on term neonatal monocyte transcription. RNA-seq was performed on term healthy and chorioamnionitis-exposed umbilical cord blood purified CD14+ monocytes under unstimulated and LPS stimulated conditions.
2018-08-01 | GSE111927 | GEO
Project description:We sought to determine the impact of chorioamnionitis exposure on the neonatal monocyte H3K4me3 histone modification landscape over the course of fetal and neonatal immune system development using ChIP-seq. H3K4me3 ChIP-seq was performed on umbilical cord blood purified CD14+ monocytes from healthy and chorioamnionitis-exposed extremely preterm neonates (under 30 weeks gestation), late preterm neonates (30-36 weeks gestation), and term neonates (37+ weeks gestation).
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Project description:Monocytes are circulating mononuclear phagocytes, poised to extravasate to sites of inflammation and differentiate into monocyte-derived macrophages and dendritic cells. Tumor necrosis factor (TNF) and its receptors are upregulated during monopoiesis and expressed by circulating monocytes, as well as effector monocytes infiltrating certain sites of inflammation, such the spinal cord during experimental autoimmune encephalomyelitis (EAE). Using competitive in vitro and in vivo assays, we show here that monocytes deficient for TNF or TNF receptors are outcompeted by their wild-type counterpart. Moreover, monocyte autonomous TNF is critical for the function of these cells, as TNF ablation in monocytes / macrophages, but not in microglia delayed the onset of EAE in challenged animals and was associated with reduced acute spinal cord infiltration of Ly6Chi effector monocytes. Collectively, our data reveal a previously unappreciated critical cell-autonomous role of TNF on monocytes for their survival, maintenance and function.
2017-04-19 | GSE94546 | GEO
Project description:We investigated the hypothesis that transmigration drives monocyte transcriptional changes. Using Agilent Whole Human Genome Microarrays, we identified over 600 differentially expressed genes (2x, p<0.05) in freshly isolated human monocytes following 1.5 h of transmigration across IL1beta-stimulated ECs compared to untreated monocytes. Genes up-regulated by monocyte transmigration belong to a number of overrepresented functional groups including immune response, and inhibition of apoptosis. qRT-PCR confirmed increased expression of monocyte chemotactic proteins 1 and 3 and of NLR family apoptosis inhibitory protein (NAIP) following monocyte transmigration. In addition, quantification of annexin V binding revealed a reduction in apoptosis following monocyte transmigration. Comparison of gene expression in transmigrated monocytes to additional controls (monocytes which failed to transmigrate and monocytes incubated beneath stimulated ECs) revealed 89 differentially expressed genes which were controlled by the physical process of diapedesis. Functional annotation of these genes showed down-regulation of antimicrobial genes (e.g. alpha-defensin down 50x, cathelicidin down 9x, and cathepsin G down 3x). qRT-PCR confirmed down-regulation of these genes. Immunoblots confirmed that monocyte transmigration down-regulates alpha-defensin protein expression. Overall, these data indicate that exposure of monocytes to stimulated ECs promotes further monocyte recruitment and inhibits monocyte apoptosis. Unexpectedly, following transmigration monocytes displayed reduced anti-microbial expression. Monocytes were allowed to transmigrate across IL1b stimulated HUVEC. Monocytes which transmigrated and monocytes which failed to transmigrate were collected after 1.5 hours from 3 experimental replicates of different human donors. Untreated monocytes were collected as a control from 4 human donors. Monocytes incubated beneath stimulated HUVEC for 1.5 hours were also collected from four human donors as a control.
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Project description:In mice, two restricted DC progenitors, macrophage-dendritic progenitor (MDP) and common dendritic cell progenitor (CDP) demonstrate increasing commitment of DC lineage as they sequentially lose granulocyte and monocyte potential respectively. Identifying these progenitors has enabled understanding of the role of DCs and monocytes in immunity and tolerance in mice. In humans, however, restricted monocyte and DC progenitors remain unknown. Progress in studying human DC development has been hampered by lack of an in vitro culture system that recapitulates in vivo DC hematopoiesis. Here we report a culture system that supports development of CD34+ hematopoietic stem cell progenitors into the three major human DC subsets, monocytes, granulocytes, NK and B cells. Using this culture system we defined the pathway for human DC development, and revealed the sequential origin of human DCs from increasingly restricted progenitors: a granulocyte-monocyte-DC progenitor (hGMDP) that develops into a monocyte-DC progenitor (hMDP) that develops into monocytes and a common DC progenitor (hCDP) that is restricted to produce the three major DC subsets. The phenotype of the DC progenitors partially overlaps with granulocyte monocyte progenitors (GMPs). These progenitors reside in human cord blood and bone marrow but not in the blood or lymphoid tissues in the steady state. We performed whole transcriptome expression analysis on monocytes and subsets of dendritic cells i.e. CD1c+ DCs, CD141+ DCs and CD303+ pDCs isolated from blood or differentiated in culture from cord blood CD34+ cells in presence of MS5 stromal cells and Flt3l, GM-CSF and SCF cytokines.
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Project description:We investigated the hypothesis that transmigration drives monocyte transcriptional changes. Using Agilent Whole Human Genome Microarrays, we identified over 600 differentially expressed genes (2x, p<0.05) in freshly isolated human monocytes following 1.5 h of transmigration across IL1beta-stimulated ECs compared to untreated monocytes. Genes up-regulated by monocyte transmigration belong to a number of overrepresented functional groups including immune response, and inhibition of apoptosis. qRT-PCR confirmed increased expression of monocyte chemotactic proteins 1 and 3 and of NLR family apoptosis inhibitory protein (NAIP) following monocyte transmigration. In addition, quantification of annexin V binding revealed a reduction in apoptosis following monocyte transmigration. Comparison of gene expression in transmigrated monocytes to additional controls (monocytes which failed to transmigrate and monocytes incubated beneath stimulated ECs) revealed 89 differentially expressed genes which were controlled by the physical process of diapedesis. Functional annotation of these genes showed down-regulation of antimicrobial genes (e.g. alpha-defensin down 50x, cathelicidin down 9x, and cathepsin G down 3x). qRT-PCR confirmed down-regulation of these genes. Immunoblots confirmed that monocyte transmigration down-regulates alpha-defensin protein expression. Overall, these data indicate that exposure of monocytes to stimulated ECs promotes further monocyte recruitment and inhibits monocyte apoptosis. Unexpectedly, following transmigration monocytes displayed reduced anti-microbial expression.
2009-11-16 | GSE14027 | GEO
Project description:Newborns, particularly those born prematurely, are extremely vulnerable to sepsis and this has been attributed to ‘immature’ innate monocyte defences. Predominant pathogens include Escherichia. coli and Staphylococcus. epidermidis but no studies have assessed global transcriptional responses of neonatal monocytes to live sepsis-causing bacteria. Here, we aimed to identify and characterise the common and pathogen-specific, neonatal monocyte transcriptional responses to E. coli and S. epidermidis to better understand early life innate immune responses. RNA-sequencing was performed on purified cord blood monocytes from very preterm (<32 weeks gestational age, GA) and term infants (37-40 weeks GA) following standardised challenge with live S. epidermidis or E. coli.
2018-03-16 | GSE101880 | GEO
Project description:Monocytes can give rise to multiple highly specialized cell types to perform a wide array of functions, ranging from pathogen phagocytosis to bone resorption. This differentiation is induced by the binding of cytokines to dedicated receptors on the surface of monocytes, which results in the initiation of genetic programs that enable cells to perform their specialized functions. Given their common background, it is not surprising that monocyte-derived cells share abilities and cellular markers, yet their specialized functions require a dedicated set of proteins. In order to dissect the monocyte differentiation process and to define cell type-specific marker proteins, we differentiated circulating monocytes into dendritic cells, M1 and M2 macrophages, and osteoclasts, and assessed their proteomes by quantitative mass spectrometry throughout the differentiation process. Statistical analysis indicated that monocyte differentiation is a linear process characterized by a common core of proteins that is similarly affected among the distinct differentiation paths. Throughout the specialization process a cluster of RNA-binding and processing proteins was downregulated whereas proteins associated to metabolic processes were increased. Analysis of the specialized cells after 10 days of differentiation uncovered existing and putative novel dendritic cell markers. Combined, we here present a comprehensive proteomic analysis of monocyte differentiation uncovering shared and distinct proteomic features of differentiating monocytes and monocyte-derived cells.
2021-09-09 | PXD016245 | Pride
Project description:Human monocytes are a heterogeneous cell population consisting of three subsets: classical CD14++CD16-, intermediate CD14++CD16+ and nonclassical CD14+CD16++ monocytes. Intermediate monocytes contribute to inflammation, and their circulating cell counts are increased in many chronic inflammatory diseases, even though the underlying pathways are poorly characterized. We tested in how far epigenetic mechanisms regulate human monocytes heterogeneity in chronic kidney disease, which is a proinflammatory condition of substantial epidemiological importance. By applying next-generation Methyl-Sequencing (Methyl-Seq) we characterized genome-wide DNA methylation within the three monocyte subsets and analyzed the impact of uremia on DNA methylation in differentiating monocytes. We found that each monocyte subset displays a unique phenotype with regards to DNA methylation. Genes with differentially methylated promoter regions in intermediate monocytes were linked to distinct immunological processes, which is in line with results from recent gene expression analyses. In vitro, uremia induced a dysregulation of DNA methylation in differentiating monocytes which affected several transcription factors important for monocyte differentiation (e.g. FLT3, HDAC1, MNT) and led to enhanced generation of intermediate monocytes. As a potential mediator, the uremic toxin and DNA methylation inhibitor S-Adenosylhomocysteine induced shifts in monocyte subsets in vitro, and associated with monocyte subset counts in vivo. In summary, our data support the concept of monocyte trichotomy and the distinct role of intermediate monocytes in human immunity. The shift in monocyte subsets which occurs in chronic kidney disease, a proinflammatory condition of substantial epidemiological impact, may be induced by the accumulation of specific uremic toxins that mediate epigenetic dysregulation.
2015-10-07 | GSE73788 | GEO
Project description:Kawasaki disease (KD) is characterized by a disorder of immune response, and its etiology remains unknown. Monocyte is an important member of body's innate immune system, however its role in KD is still elusive due to its ambiguous heterogeneity and complex functions. Here, scRNA-seq was performed to reveal monocytes heterogeneity in healthy and KD infants. Circulating monocytes were separated from peripheral blood and scRNA-seq was used to transcriptionally profile the monocytes in both healthy and KD infants. Four monocyte subsets are identified in infants, in which three clusters are mainly CD14+CD16- monocytes and one cluster is mainly CD14-CD16+ monocytes. The four monocyte subsets possess different biological functions and represent a relatively linear differentiation. CD14+ monocyte subsets in KD are distinct from that of healthy infants, including one subset expressing FOLR3, S100A12 and IL1R2 and the other expressing MT-TN specifically. Moreover, the CD14+ monocyte subsets in KD are poorly differentiated, and their functions mainly involve neutrophil activation. In conclusion, a relatively comprehensive map of circulating monocyte subsets was plotted for the first time in healthy infants. CD14+ monocyte subsets that are distinct from healthy infants were revealed in KD, which may serve as a target for KD treatment in the future.
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