...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Oncomir miR-125b regulates hematopoiesis by targeting the gene Lin28A
【24h】

Oncomir miR-125b regulates hematopoiesis by targeting the gene Lin28A

机译：Oncomir miR-125b通过靶向基因Lin28A来调节造血作用

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

MicroRNA-125b (miR-125b) is up-regulated in patients with leukemia.Overexpression of miR-125b alone in mice causes a very aggressive, transplantable myeloid leukemia. Before leukemia, these mice do not display elevation of white blood cells in the spleen or bone marrow;rather, the hematopoietic compartment shows lineage-skewing, with myeloid cell numbers dramatically increased and B-cell numbers severely diminished. miR-125b exerts this effect by up-regulating the number of common myeloid progenitors while inhibiting development of pre-B cells. We applied a miR-125b sponge loss of function system in vivo to show that miR-125b physiologically regulates hematopoietic development. Investigating the mechanism by which miR-125b regulates hematopoiesis, we found that, among a panel of candidate targets, the mRNA for Lin28A, an induced pluripotent stem cell gene, was most repressed by miR-125b in mouse hematopoietic stem and progenitor cells. Overexpressing Lin28A in the mouse hematopoietic system mimicked the phenotype observed on inhibiting miR-125b function, leading to a decrease in hematopoietic output.Relevant to the miR-125b overexpression phenotype, we also found that knockdown of Lin28A led to hematopoietic lineage-skewing,with increased myeloid and decreased B-cell numbers. Thus, the miR-125b target Lin28A is an important regulator of hematopoiesis and a primary target of miR-125b in the hematopoietic system.
机译：白血病患者中的microRNA-125b（miR-125b）上调.miR-125b在小鼠中的过度表达会引起非常具有侵略性的可移植的骨髓性白血病。在白血病之前，这些小鼠的脾脏或骨髓中的白细胞没有升高；相反，造血区室显示出谱系偏移，髓样细胞数量急剧增加，B细胞数量严重减少。 miR-125b通过上调常见骨髓祖细胞的数量而发挥作用，同时抑制前B细胞的发育。我们在体内应用了miR-125b海绵功能丧失系统，以显示miR-125b在生理上调节造血发育。研究miR-125b调节造血作用的机制后，我们发现，在一组候选靶标中，miR-125b在小鼠造血干细胞和祖细胞中对诱导的多能干细胞基因Lin28A的mRNA的抑制作用最大。小鼠造血系统中过表达的Lin28A模仿了抑制miR-125b功能的表型，导致造血输出的减少。与miR-125b过表达的表型相关，我们还发现Lin28A的敲低导致造血谱系的偏斜，伴随着髓样细胞增多，B细胞数量减少。因此，miR-125b靶标Lin28A是造血系统的重要调节剂，也是造血系统中miR-125b的主要靶标。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号