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Clonal dominance of hematopoietic stem cells triggered by retroviral gene marking.
- Source :
-
Science (New York, N.Y.) [Science] 2005 May 20; Vol. 308 (5725), pp. 1171-4. - Publication Year :
- 2005
-
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.
- Subjects :
- Animals
Antigens, CD34 genetics
Bone Marrow Transplantation
DNA-Binding Proteins genetics
Down-Regulation
Humans
Ligase Chain Reaction
MDS1 and EVI1 Complex Locus Protein
Mice
Mice, Inbred C57BL
Polymerase Chain Reaction
Proto-Oncogenes genetics
Transcription Factors genetics
Transcription, Genetic
Transgenes
Up-Regulation
Genetic Vectors
Hematopoiesis
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells physiology
Mutagenesis, Insertional
Retroviridae genetics
Virus Integration
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9203
- Volume :
- 308
- Issue :
- 5725
- Database :
- MEDLINE
- Journal :
- Science (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 15905401
- Full Text :
- https://doi.org/10.1126/science.1105063