...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Transfusion: The Journal of the American Association of Blood Banks >SALL4 is a key transcription regulator in normal human hematopoiesis
【24h】

SALL4 is a key transcription regulator in normal human hematopoiesis

机译：SALL4是正常人类造血过程中的关键转录调节因子

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

BACKGROUND: Stem cell factor SALL4 is a zinc finger transcription factor. It plays vital roles in the maintenance of embryonic stem cell properties, functions as an oncogene in leukemia, and has been recently proposed to use for cord blood expansion. The mechanism(s) by which SALL4 functions in normal human hematopoiesis, including identification of its target genes, still need to be explored. STUDY DESIGN AND METHODS: Chromatin immunoprecipitation followed by microarray hybridization (ChIP-chip) was used for mapping SALL4 global gene targets in normal primary CD34+ cells. The results were then correlated with SALL4 functional studies in the CD34+ cells. RESULTS: More than 1000 potential SALL4 downstream target genes have been identified, and validation of binding by ChIP-quantitative polymerase chain reaction was performed for 5% of potential targets. These include genes that are involving in hematopoietic differentiation and self-renewal, such as HOXA9, RUNX1, CD34, and PTEN. Down regulation of SALL4 expression using small-hairpin RNA in these cells led to decreased in vitro myeloid colony-forming abilities and impaired in vivo engraftment. Furthermore, HOXA9 was identified to be a major SALL4 target in normal human hematopoiesis and the loss of either SALL4 or HOXA9 expression in CD34+ cells shared a similar phenotype. CONCLUSION: Taken together, SALL4 is a key regulator in normal human hematopoiesis and the mechanism of its function is at least in part through the HOXA9. Future study will determine whether modulating the SALL4/HOXA9 pathway can be used in cellular therapy such as cord blood expansion and/or myeloid engraftment.
机译：背景：干细胞因子SALL4是锌指转录因子。它在维持胚胎干细胞特性中起着至关重要的作用，在白血病中起癌基因的作用，最近已被提议用于脐带血扩增。 SALL4在正常人类造血中起作用的机制，包括其靶基因的鉴定，仍需要探索。研究设计和方法：使用染色质免疫沉淀，然后进行微阵列杂交（ChIP芯片）来定位正常原代CD34 +细胞中的SALL4全局基因靶标。然后将结果与CD34 +细胞中的SALL4功能研究相关。结果：已鉴定出1000多个潜在的SALL4下游靶基因，并通过ChIP定量聚合酶链反应对5％的潜在靶进行了结合验证。这些包括涉及造血分化和自我更新的基因，例如HOXA9，RUNX1，CD34和PTEN。在这些细胞中使用小发夹RNA来下调SALL4的表达会导致体外髓样集落形成能力下降，并损害体内植入。此外，HOXA9被确定为正常人造血中的主要SALL4靶标，并且CD34 +细胞中SALL4或HOXA9表达的丧失具有相似的表型。结论：SALL4是正常人造血的关键调节剂，其功能机制至少部分是通过HOXA9引起的。未来的研究将确定调节SALL4 / HOXA9途径是否可用于细胞治疗，例如脐带血扩增和/或骨髓植入。

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