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For the first time, researchers from the Hematology Hospital of the Chinese Academy of Medical Sciences (the Institute of Hematology of the Chinese Academy of Medical Sciences), Peking University and Harvard University in the United States systematically depict for the first time the dynamic changes of heterogeneous groups and transcription groups in the maturation, differentiation and destiny decision of neutrophil cells in steady state and inflammatory state, integrating the heterogeneity classification of neutrophils in existing fields, providing valuable reference data resources for the further study of neutrophils. On July 27,
, the paper was published online in Nature-Immune.
neutrophils are the main components of the natural immune system, as the largest number of circulating white blood cells in the cell type, is the host's first line of defense against invasive bacteria and other pathogens.
However, at present, the sub-group of neutrophils mainly relies on classical morphology, and the heterogeneous nature of neutrophils has always been controversial.
the number and level of gene expression in neutrophils is low compared to other blood and immune cell types, and RNA capture is technically more difficult.
, because the half-life of neutrophils is only 15 to 20 hours, the details of the experimental operation also put forward higher requirements.
the researchers performed neutrophil isolation and single-cell RNA sequencing on the bone marrow, peripheral blood and spleen in the stable state of mice by optimizing the experimental conditions, and established a neutrophil single-cell map under steady state conditions in combination with bioinformatics.
in the order of maturation, the neutrophils in the bone marrow can be divided into 5 groups, including 3 subgroups in the division stage and two more mature subgroups after division.
researchers analyzed the characteristics of each group in detail for granulocytes, cell cycles, and bactericidal function, and verified the presence of these groups in combination with flow cell markers.
results show that although the heterogeneous cell population defined by single-cell RNA sequencing has a high correlation with the classical morphological credit group as a whole, single-cell sequencing techniques can identify more mature subgroup cell populations with the same morphology and different transcription groups, which increase the understanding of the heterogeneity of the mature granulocytes of bone marrow.
based on the heterogeneity expressed between the groups of granule gene genes, the researchers also proposed a "sorting hypothesis" for the production of granulocytes, and identified a new transcription factor that is specifically raised during the development of neutrophils through transcription control network analysis.
, the researchers further validated the unique spatial distribution of mature neutrophils in the spleen with high-expression interferon stimulation of the gene, suggesting that the subgroup may have host defenses that differ from other subgroups.
they also found that the heterogeneous population of neutrophils in inflammatory states did not change, but there were significant changes in the proportion of groups, functional characteristics, transcription factor expression, and group transformation pathways.
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