Translational Research Institute, Henan Provincial People's Hospital, Academy of Medical Science, Zhengzhou University, Wei Wu Road, Jinshui District, Zhengzhou 450003, China.
Institute of Hematology, Henan Key Laboratory of Stem Cell Clinical Application and Key Technology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Wei Wu Road, Jinshui District, Zhengzhou 450003, China.
J Leukoc Biol. 2024 Oct 1;116(4):909-914. doi: 10.1093/jleuko/qiae128.
Loss and overexpression of FAT1 occurs among different cancers, with these divergent states equated with tumor suppressor and oncogene activity, respectively. Regarding the latter, FAT1 is highly expressed in a high proportion of human acute leukemias relative to normal blood cells, with evidence pointing to an oncogenic role. We hypothesized that this occurrence represents legacy expression of FAT1 in undefined hematopoietic precursor subsets (i.e. sustained following transformation), predicating a role for FAT1 during normal hematopoiesis. We explored this concept by using the Vav-iCre strain to construct conditional knockout mice in which Fat1 expression was deleted at the hematopoietic stem cell stage. Extensive analysis of precursor and mature blood populations using multipanel flow cytometry revealed no ostensible differences between Fat1 conditional knockout mice and normal littermates. Further functional comparisons involving colony-forming unit and competitive bone marrow transplantation assays support the conclusion that Fat1 is dispensable for normal murine hematopoiesis.
FAT1 的缺失和过表达存在于不同的癌症中，分别与肿瘤抑制基因和癌基因活性相关。关于后者，FAT1 在相对于正常血细胞的高比例的人类急性白血病中高度表达，有证据表明其具有致癌作用。我们假设这种情况代表 FAT1 在未定义的造血前体细胞亚群中的遗留表达（即在转化后持续存在），这预示着 FAT1 在正常造血过程中的作用。我们使用 Vav-iCre 株来构建条件性敲除小鼠，在造血干细胞阶段删除 Fat1 表达，从而探索了这一概念。使用多面板流式细胞术对前体细胞和成熟血细胞进行广泛分析，并未发现 Fat1 条件性敲除小鼠与正常同窝仔鼠之间存在明显差异。涉及集落形成单位和竞争性骨髓移植实验的进一步功能比较支持 Fat1 对于正常小鼠造血是可有可无的结论。
