Distinct responses of newly identified monocyte subsets to advanced gastrointestinal cancer and COVID-19
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ABSTRACT:
PROVIDER: PRJNA878760 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21502006.fastq.gz | Fastqsanger.gz | |||
| SRR21502007.fastq.gz | Fastqsanger.gz | |||
| SRR21502008.fastq.gz | Fastqsanger.gz | |||
| SRR21502009.fastq.gz | Fastqsanger.gz | |||
| SRR21502010.fastq.gz | Fastqsanger.gz |
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Project description:Monocytes are critical cells of the immune system but their role as effectors is relatively poor understood, as they have long been considered only as precursors of tissue macrophages or dendritic cells. Moreover, it is known that this cell type is heterogeneous, but our understanding of this aspect is limited to the broad classification in classical/intermediate/non-classical monocytes, commonly based on their expression of only two markers, i.e. CD14 and CD16. We deeply dissected the heterogeneity of human circulating monocytes in healthy donors by transcriptomic analysis at single-cell level and identified 9 distinct monocyte populations characterized each by a profile suggestive of specialized functions. The classical monocyte subset in fact included five distinct populations, each enriched for transcriptomic sets related to either inflammatory, neutrophil-like, interferon-related, and platelet-related pathways. Non-classical monocytes included two distinct populations, one of which marked specifically by elevated expression levels of complement components. Intermediate monocytes were not further divided in our analysis and were characterized by high levels of HLA genes. Finally, we identified one cluster included in both classical and non-classical monocytes, characterized by a strong cytotoxic signature. These findings provided the rationale to exploit the relevance of newly identified monocyte populations in disease evolution. Collectively, this study unravels an unexpected complexity among human circulating monocytes.
2022-10-04 | GSE213004 | GEO
Project description:Monocytes are critical cells of the immune system but their role as effectors is relatively poorly understood, as they have long been considered only as precursors of tissue macrophages or dendritic cells. Moreover, it is known that this cell type is heterogeneous, but our understanding of this aspect is limited to the broad classification in classical/intermediate/non-classical monocytes, commonly based on their expression of only two markers, i.e. CD14 and CD16. We deeply dissected the heterogeneity of human circulating monocytes in healthy donors by transcriptomic analysis at single-cell level and identified 9 distinct monocyte populations characterized each by a profile suggestive of specialized functions. The classical monocyte subset in fact included five distinct populations, each enriched for transcriptomic gene sets related to either inflammatory, neutrophil-like, interferon-related, and platelet-related pathways. Non-classical monocytes included two distinct populations, one of which marked specifically by elevated expression levels of complement components. Intermediate monocytes were not further divided in our analysis and were characterized by high levels of human leukocyte antigen (HLA) genes. Finally, we identified one cluster included in both classical and non-classical monocytes, characterized by a strong cytotoxic signature. These findings provided the rationale to exploit the relevance of newly identified monocyte populations in disease evolution. A machine learning approach was developed and applied to two single-cell transcriptome public datasets, from gastrointestinal cancer and Coronavirus disease 2019 (COVID-19) patients. The dissection of these datasets through our classification revealed that patients with advanced cancers showed a selective increase in monocytes enriched in platelet-related pathways. Of note, the signature associated with this population correlated with worse prognosis in gastric cancer patients. Conversely, after immunotherapy, the most activated population was composed of interferon-related monocytes, consistent with an upregulation in interferon-related genes in responder patients compared to non-responders. In COVID-19 patients we confirmed a global activated phenotype of the entire monocyte compartment, but our classification revealed that only cytotoxic monocytes are expanded during the disease progression. Collectively, this study unravels an unexpected complexity among human circulating monocytes and highlights the existence of specialized populations differently engaged depending on the pathological context.
| S-EPMC9576306 | biostudies-literature
Project description:Monocytes and their lineage descendants serve as a central defense system against infection and injury but if uncontrolled can also promote an excessive pathological inflammatory response. Therefore a current research goal is to understand how the organism controls the number and function of monocytes and how these variables can be tailored in therapy. Considering the evidence that monocytes are heterogeneous and exist in at least two subsets committed to divergent functions, we investigated whether distinct factors regulate the balance between monocyte subset responses in vivo. Here we investigate the differential expression of mRNA among murine steady-state monocyte subsets. Blood was drawn from healthy C57BL/6 donors. For each biological replicate 1000 monocytes of the Ly-6Chi and Ly-6Clo phenotype were isolated from the blood sample through fluorescence activated cell sorting.
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2021-03-24 | GSE152450 | GEO
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2012-04-06 | GSE32364 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE35457: Transcriptome profiles of mouse and human monocyte and dendritic cell subsets (human data) GSE35458: Transcriptome profiles of mouse and human monocyte and dendritic cell subsets (mouse data) Refer to individual Series
2012-07-11 | E-GEOD-35459 | biostudies-arrayexpress
Project description:We used the high dimensionality of mass cytometry together with the FlowSOM clustering algorithm to accurately identify and define monocyte subsets in blood of healthy human subjects and those with coronary artery disease (CAD). To study the behavior and functionality of the newly defined monocyte subsets, we performed RNA sequencing, transwell migration, and efferocytosis assays. Here, we identify 8 human monocyte subsets based on their surface marker phenotype. We found that 3 of these subsets fall within the CD16+ nonclassical monocyte population and 4 subsets belong to the CD14+ classical monocytes, illustrating significant monocyte heterogeneity in humans. As nonclassical monocytes are important in modulating atherosclerosis in mice, we studied the functions of our 3 newly identified nonclassical monocytes in subjects with CAD. We found a marked expansion of a Slan+CXCR6+ nonclassical monocyte subset in CAD subjects, which was positively correlated with CAD severity. This nonclassical subset can migrate towards CXCL16 and shows an increased efferocytosis capacity, indicating it may play an atheroprotective role.
2020-03-06 | GSE146447 | GEO
Project description:Human and mouse blood each contain two monocyte subsets. Here, we investigated the extent of their similarity using a microarray approach. Approximately 300 genes in human and 550 genes in mouse were differentially expressed between subsets. More than 130 of these gene expression differences were conserved between mouse and human monocyte subsets. We confirmed numerous differences at the cell surface protein level. Despite overall conservation, some molecules were conversely expressed between the two species’ subsets, including CD36, CD9, and TREM-1. Furthermore, other differences existed, including a prominent PPARγ signature in mouse monocytes absent in human. Overall, human and mouse monocyte subsets are far more broadly conserved than currently recognized. Thus, studies in mice may indeed yield relevant information regarding the biology of human monocyte subsets. However, differences between the species deserve consideration in models of human disease studied in the mouse. The two major subsets of monocytes (Ly-6C+ and Ly-6Clo) from 12-week old C57Bl/6 mice were sorted and the RNA extracted and hybridized to Affymetrix GeneChip® 430 2.0 arrays. We pooled leukocytes from 5 mice for each sort and sorted 4 separate times for 4 biological replicates. The two major monocyte subsets (CD16- and CD16+) were isolated from venous heparinized blood from apparently healthy human volunteers using MACS technology with all reagents and tools from Miltenyi Biotec. Three separate donors were hybridized three different times to Affymetrix U133 Plus 2.0 array.
2009-12-03 | E-GEOD-17256 | biostudies-arrayexpress
Project description:Human and mouse blood each contain two monocyte subsets. Here, we investigated the extent of their similarity using a microarray approach. Approximately 300 genes in human and 550 genes in mouse were differentially expressed between subsets. More than 130 of these gene expression differences were conserved between mouse and human monocyte subsets. We confirmed numerous differences at the cell surface protein level. Despite overall conservation, some molecules were conversely expressed between the two speciesM-bM-^@M-^Y subsets, including CD36, CD9, and TREM-1. Furthermore, other differences existed, including a prominent PPARM-NM-3 signature in mouse monocytes absent in human. Overall, human and mouse monocyte subsets are far more broadly conserved than currently recognized. Thus, studies in mice may indeed yield relevant information regarding the biology of human monocyte subsets. However, differences between the species deserve consideration in models of human disease studied in the mouse. Keywords: Expression profiling by array The two major subsets of monocytes (Ly-6C+ and Ly-6Clo) from 12-week old C57Bl/6 mice were sorted and the RNA extracted and hybridized to Affymetrix GeneChipM-BM-. 430 2.0 arrays. We pooled leukocytes from 5 mice for each sort and sorted 4 separate times for 4 biological replicates. The two major monocyte subsets (CD16- and CD16+) were isolated from venous heparinized blood from apparently healthy human volunteers using MACS technology with all reagents and tools from Miltenyi Biotec. Three separate donors were hybridized three different times to Affymetrix U133 Plus 2.0 array.
2009-12-07 | E-GEOD-18565 | biostudies-arrayexpress
Project description:Gene expression profile of primary human monocyte subsets
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