...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Hepatology: Official Journal of the American Association for the Study of Liver Diseases >Systems Biological Analyses Reveal the Hepatitis C Virus (HCV)-Specific Regulation of Hematopoietic Development
【24h】

Systems Biological Analyses Reveal the Hepatitis C Virus (HCV)-Specific Regulation of Hematopoietic Development

机译：系统生物学分析揭示丙型肝炎病毒（HCV）的造血发育的特定监管。

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

Chronic liver disease is characterized by the liver enrichment of myeloid dendritic cells (DCs). To assess the role of disease on myelopoiesis, we utilized a systems biology approach to study development in liver-resident cells expressing stem cell marker CD34. In patients with endstage liver disease, liver CD34+ cells were comprised of two subsets, designated CD34+CD146+ and CD34+CD146-, and hematopoietic function was restricted to CD34+CD146- cells. Liver CD34 frequencies were reduced during nonalcoholic steatohepatitis (NASH) and chronic hepatitis C virus (HCV) compared to alcohol liver disease (ALD), and this reduction correlated with viral load in the HCV cohort. To better understand the relationship between liver CD34+CD146+ and CD34+CD146- subsets and any effects of disease on CD34 development, we used gene expression profiling and computational modeling to compare each subset during ALD and HCV. For CD34+CD146+ cells, increased expression of endothelial cell genes including von Willebrand factor, VE-cadherin, and eNOS were observed when compared to CD34+CD146- cells, and minimal effects of ALD and HCV diseases on gene expression were observed. Importantly for CD34+CD146- cells, chronic HCV was associated with a distinct imprint of programs related to cell cycle, DNA repair, chemotaxis, development, and activation, with an emphasis on myeloid and B lymphocyte lineages. This HCV signature was further translated in side-by-side analyses, where HCV CD34+CD146- cells demonstrated superior hematopoietic growth, colony formation, and diversification compared to ALD and NASH when cultured identically. Disease-associated effects on hematopoiesis were also evident by phenotypic alterations in the expression of CD14, HLA-DR, and CD16 by myeloid progeny cells. Conclusion: Etiology drives progenitor fate within diseased tissues. The liver may be a useful source of hematopoietic cells for therapy, or as therapeutic targets. (Hepatology 2015;61:843-856)
机译：慢性肝病的特征在于肝脏中髓样树突状细胞（DC）的富集。为了评估疾病对骨髓生成的作用，我们利用系统生物学方法研究了表达干细胞标记CD34的肝驻留细胞的发育。在患有晚期肝病的患者中，肝脏CD34 +细胞由两个亚群组成，分别称为CD34 + CD146 +和CD34 + CD146-，并且造血功能仅限于CD34 + CD146-细胞。与酒精性肝病（ALD）相比，非酒精性脂肪性肝炎（NASH）和慢性丙型肝炎病毒（HCV）期间的肝CD34频率降低，并且这种降低与HCV队列中的病毒载量相关。为了更好地了解肝脏CD34 + CD146 +和CD34 + CD146-子集之间的关系以及疾病对CD34发育的任何影响，我们使用了基因表达谱分析和计算模型来比较ALD和HCV期间的每个子集。对于CD34 + CD146 +细胞，与CD34 + CD146-细胞相比，观察到内皮细胞基因包括von Willebrand因子，VE-钙粘着蛋白和eNOS的表达增加，并且ALD和HCV疾病对基因表达的影响最小。重要的是对于CD34 + CD146-细胞，慢性HCV与细胞周期，DNA修复，趋化性，发育和激活相关的程序具有独特的烙印，重点是髓样和B淋巴细胞谱系。 HCV标记在并排分析中进一步翻译，其中当相同培养时，与ALD和NASH相比，HCV CD34 + CD146-细胞显示出优异的造血生长，集落形成和多样化。骨髓后代细胞CD14，HLA-DR和CD16表达的表型改变也证明了与造血相关的疾病相关作用。结论：病因驱动患病组织内祖细胞的命运。肝脏可能是用于治疗或作为治疗靶点的造血细胞的有用来源。 （肝病2015; 61：843-856）

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