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Researchers from the Hospital of Hematology of the Chinese Academy of Medical Sciences (Institute of Hematology of the Chinese Academy of Medical Sciences), Peking University and Harvard University in the United States systematically described for the first time the dynamic changes of heterogeneous groups and transcriptomes in the process of heterogeneous groups and transcriptional groups of neutral granulocytes in stable and inflammatory states from a single-cell scale, integrating existing classifications of neutral cytocytes in the field, providing valuable reference data resources for further research on neutrocytes. On July 27th, the paper was published online in Nature - Immunity.
neutral granulocytes are the main component of the natural immune system, as the largest number of circulating white blood cells in the cell type, is the host against invasive bacteria and other pathogens the first line of defense. However, at present, the group of neutral granulocytes mainly depends on classical morphology, the heterogeneity of neutral granulocytes has been controversial. Compared with other blood and immune cell types, the number and level of gene expression in neutral granulocytes is low, and the technical capture of RNA is more difficult. In addition, since the half-life of neutral granulocytes is only 15 to 20 hours, the details of experimental operation are also higher requirements.
researchers performed neutral granulocyte separation and single-cell RNA sequencing on bone marrow, perennial blood and spleen in mice by optimizing experimental conditions, and combined bio-informational methods to establish a single-cell map of neutral granules under steady state conditions.
in the order of maturation, the neutral granulocytes in the bone marrow can be divided into 5 groups, including 3 sub-groups in the division stage and 2 more mature sub-groups after division. The researchers analyzed the characteristics of each group in detail for particle protein, cell cycle, sterilization function, etc., and verified the existence of these groups by combining 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, the single-cell sequencing technique can identify the more mature subgroup granulocyte population with the same morphology and differences in transcription group, which increases the understanding of heterogeneity of mature granulocytes in bone marrow.
Based on the heterogeneity of particle protein genes expressed between subpopulations, the researchers also proposed the "picking hypothesis" of particle protein production, and identified new transcription factors specifically increased during the development of neutral granulocytes through transcriptional regulation network analysis.
In addition, the researchers further validated the unique spatial distribution of mature neutral granulocytes in the spleen of genes associated with high expression interferon stimulation, suggesting that the sub-group may have host defense functions that are different from those of other sub-groups. They also found no change in the heterogeneity of heterogeneity of neutral granulocytes in the inflammatory state, but significant changes in the proportion of populations, functional characteristics, transcription factor expression, and group transformation pathways. (Source: Lu Yi, China Science Journal)
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