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    Home > Biochemistry News > Biotechnology News > Single-cell map reveals drug resistance mechanism for ulcerative colitis

    Single-cell map reveals drug resistance mechanism for ulcerative colitis

    • Last Update: 2020-06-17
    • Source: Internet
    • Author: User
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    Screenshot from the Irish Post's official websiteit's hard to imagine Dillon's pain for anyone who doesn't know ulcerative colitisUlcerative colitis (UC) is a chronic, progressive, inflammatory intestinal diseaseUC patients often suffer from abdominal pain, accompanied by persistent diarrhea, and may even develop rectal bleeding and weight lossThere are about 907,000 UC patients in the United States and about 1 million UC patients in EuropeHowever, it is not clear what the pathogenesis behind ulcerative colitis isEven UC patients with the same diagnosis may have very different reactions to treatment, researchers at the Massachusetts Institute of Technology and Harvard University recently explored how changes in intestinal tissue composition and interactions between different cell types affect disease through a high-list cell map of ulcerative colitis, and identified the role of disease-related cells and pathway genes in thisThis single-cell map provides a solid foundation for improving the level of diagnostic treatment in UC patientsThe findings were published in the journal CellDOI:lead author of the study, Christopher Smillie, Moshe Biton, and Jos? Ordovas-Monta?es, in order to understand cell type specificity and pathways, generated a map of 366,650 cells from 18 UC patients and 12 healthy humancolon mucous membranes, revealing 51 epithelial cells, matrix cells, and immune cell subgroupsmultiple cell groupsstudy compared tissue samples from UC patients and healthy individuals, and showed that many UC risk genes were cell-specific and subject to relatively few gene regulatory pathwaysThis indicates significant differences in the proportion of certain cells and their possible interactionsFor example, in UC patient samples, a particular type of fibroblasts associated with inflammation and T-cells that simultaneously express CD8 and IL-17 were more likely to be representeda snapshot of T cells that express CD4 (green), CD8 (white) and IL-17 (red) in inflamed colon tissue
    the team also found a rare cluster of epithelial cells called microfibrocells (microfibre-like cells)The cells are usually found only in the small intestine, but they are also found in the colons of UC patientsresearchers found that multiple cell groups send signals to each other and control other interactions between different cell subgroupsThis indicates that there has been a significant recombination of the cellular network in the diseased colonnew explanation for the resistance to ulcerative colitis
    study data suggest that new cell subgroups may be associated with drug resistance, which affects about one-third of patients, or may be associated with other genes that increase the risk of ulcerative colitisThe researchers then gained further insight into the possible mechanisms of drug resistance in patients with ulcerative colitisin UC patients, tumor necrosis factor (TNF) protein levels are high, and anti-TNF drugs reduce inflammation and heal tissue in many patientsHowever, about 30 percent of patients did not respond to treatment, and those who responded became resistant over timeresearchers have previously identified the genes associated with drug resistance, but it is not clear which specific cell types in the colon express themIAFs and mononucleocytes are associated with anti-tnf resistance through the OSM signaling pathway
    in this study, single-cell data analysis showed that one of the culprits of drug resistance was inflammation-related fibroblastsThe study identified the possibility that fibroblasts may interact with other cells to promote drug resistance and induce fibroblasts to react to a signaling molecule called OSM, bypassing the TNF pathway to develop resistanceone day, the discovery could be used to help identify patients who may be resistant to drug resistancePatients with these drug-resistant markers can be diagnosed earlyIt may also be possible to treat these specific cells in combination with drugs associated with anti-TNF therapy the genetic mapping of human cells the study is part of the International Human Cell Mapping Project Previous genetic studies in patients with ulcerative colitis have found many disease-related areas of the genome, but researchers often don't know which cells and pathways these genes play in, which hinders their further research new cell maps help researchers determine the type of cells that express these genes and their possible function The cell map also provides a general guide to determining which cell subgroups express genetic variations related to other diseases Source: 's Single-cell Atlas snobs underlying building blocks of the ulcerative colitis
    Single-cell map reveals drug resistance mechanism for ulcerative colitis
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