Kustikova Olga, Fehse Boris, Modlich Ute, Yang Min, Düllmann Jochen, Kamino Kenji, von Neuhoff Nils, Schlegelberger Brigitte, Li Zhixiong, Baum Christopher
Bone Marrow Transplantation, University Hospital Eppendorf, Martinistrasse 52, 20251 Hamburg, Germany.
Science. 2005 May 20;308(5725):1171-4. doi: 10.1126/science.1105063.
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.
使用复制缺陷型逆转录病毒载体进行基因标记已超过20年，用于追踪细胞克隆在体内的命运。我们证明，逆转录病毒整合本身可能会在小鼠长期造血过程中引发非恶性克隆性扩增。从连续移植受体中占主导地位的克隆中回收的所有29个插入片段都影响了在造血干细胞自我更新或存活中已确立或潜在起作用的基因座。在所分析的所有12个插入位点均发生了转录失调。这些发现对诊断性基因标记以及调控干细胞更新的基因的发现具有重要意义。
