Clonal dominance of hematopoietic stem cells triggered by retroviral gene marking

  • Olga Kustikova (Geteilte/r Erstautor/in)
  • Boris Fehse (Geteilte/r Erstautor/in)
  • Ute Modlich
  • Min Yang
  • Jochen Düllmann
  • Kenji Kamino
  • Nils von Neuhoff
  • Brigitte Schlegelberger
  • Zhixiong Li
  • Christopher Baum

Abstract

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.

Bibliografische Daten

OriginalspracheEnglisch
ISSN0036-8075
DOIs
StatusVeröffentlicht - 20.05.2005
PubMed 15905401