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Recently, Wang Qianfei Research Group, A key laboratory of precision genomics medicine at the Beijing Genomics Research Institute of the Chinese Academy of Sciences, collaborated with Cheng Linxuan, a professor at Johns Hopkins University School of Medicine in the United States, to reveal that NOTCH4 is the target gene for the transcription factor RUNX1 to regulate the development of in vitro macronuclear cells and to screen out small molecule inhibitors that promote in vitro macronuclear cell regeneration.
the study found new targets for in vitro macronuclear cell regeneration and proposed new ideas for finding regenerative targets using rare diseases, the study was published in the journal Blood.
, the pharmaceutical use of the new target, NOTCH4, and its inhibitors has been applied for domestic and international patents.
macronuclear cells (MKs) are highly multi-personalized and efficiently producing platelets in the bone marrow, which play an important role in hemostatic, wound healing, and maintaining the body's steady state.
transcription factor RUNX1 single allele gene embryo mutation synthasitogenescan syllabic disorders that cause MK developmental disorders and platelet reduction of familial platelet disease (FPD), but the specific mechanism is not clear.
the early study of Cheng Linyi found that the in vitro model of pluripotent stem cells (hiPSCs) sourced from FPD patients can reproduce the patient's phenotype, while the ability to generate their macronuclear cells can be restored by genetic targeting to repair the RUNX1 mutation.
in order to reveal the pathogenesis of FPD macronuclear development disorders and platelet reduction, and to promote in vitro macronuclear cell/platelet regeneration, Wang Qianfei Research Group used disease stem cell in vitro model binding functional genomics, and found a series of target genes and pathways regulated by RUNX1 and playan yin in the formation of macronuclear cells.
studies have revealed for the first time that NOTCH4, as a direct target gene for transcription factor RUNX1, is negatively regulated in vitro macronuclear cell development, and screenings for small molecular inhibitors of the Notch pathway, resulting in a nearly tenfold increase in the production of hematopoietic cells from pluripotent stem cells and umbilical blood sources.
the research results are expected to be applied to clinical infusions, the treatment of a variety of clotting dysfunction diseases, including platelet reduction, tumor chemotherapy, surgical trauma bleeding, etc., has high scientific significance and clinical value.
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