Clonal dominance of hematopoietic stem cells triggered by retroviral gene marking
Clonal dominance of hematopoietic stem cells triggered by retroviral gene marking
复制标题
DOI：
10.1126/science.1105063
复制
发表时间：
2005-05-20
期刊：
影响因子：
56.9
通讯作者：
Baum, C
中科院分区：
文献类型：
--
作者：
Kustikova, O;Fehse, B;Baum, C
使用复制缺陷型逆转录病毒载体的基因标记已被用于跟踪细胞克隆的体内命运超过20年。我们证明，逆转录病毒的整合本身可能会引发非恶性克隆小鼠长期造血扩增。从连续移植受体中占主导地位的克隆中回收的所有29个插入影响了在造血干细胞的自我更新或存活中具有既定或潜在作用的位点。在分析的所有12个插入位点中均发生转录失调。这些发现对诊断基因标记和发现调节干细胞更新的基因具有重要意义。
Gene marking with replication-defective retroviral vectors has been used for more than 20 years to track the in vivo fate of cell clones. We demonstrate that retroviral integrations themselves may trigger nonmalignant clonal expansion in murine long-term hematopoiesis. All 29 insertions recovered from clones dominating in serially transplanted recipients affected loci with an established or potential role in the self-renewal or survival of hematopoietic stem cells. Transcriptional dysregulation occurred in all 12 insertion sites analyzed. These findings have major implications for diagnostic gene marking and the discovery of genes regulating stem cell turnover.