诱发克隆性造血 z-bo 2020-10-22 314

　　Recently, a research report entitled "Inherited causes of clonal haematopoiesis in 97, 691 whole genomes" was published in the international journal Nature. Genome analysis revealed the genetic causes of clonal haematopoiesis.

　　Age is the main risk factor that induces most chronic diseases in humans, but researchers currently do not know the molecular mechanism behind the disease risk mediated by aging; in the regenerative hematopoietic stem cell population, the acquisition of age-related somatic mutations can lead to cloning This has recently been confirmed to be directly related to the occurrence of human blood cancers and coronary heart disease. This phenomenon is called "CHIP, clonal haematopoiesis of indeterminate potential" (CHIP); the germ line is also analyzed The whole genome sequence data of somatic cells may provide certain ideas and opportunities for revealing the root cause of CHIP.

　　In this study, researchers analyzed 97,691 individuals from different ancestors from the National Heart, Lung and Blood Institute's Precision Medicine Interomics (TOPMed) project with high coverage of the whole genome sequence, and finally identified 4229. Individuals with CHIP status. In the article, the researchers determined the associations between blood cells, lipid properties, and inflammatory features that are very specific to different CHIP driver genes, and finally discovered a set of genome-wide germline genetic mutations that can help researchers identify and There are three genetic loci related to CHIP status, including TET2 locus, which is unique to individuals of African descent.

　　Researchers said that in vitro evaluation of TET2 germline sites may help to effectively identify mutations that interfere with the function of the distal enhancer of TET2. The interference of the distal enhancer of TET2 will increase the level of self-renewal of hematopoietic stem cells. Generally speaking, in this study, researchers have observed how germline genetic mutations shape the function of hematopoietic stem cells, thereby inducing the formation of CHIP, which may be through a specific mechanism of cloning hematopoiesis and a mechanism that leads to different tissues. The shared mechanism of cell mutation is realized.