Publication Date:
2005-05-21
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kustikova, Olga -- Fehse, Boris -- Modlich, Ute -- Yang, Min -- Dullmann, Jochen -- Kamino, Kenji -- von Neuhoff, Nils -- Schlegelberger, Brigitte -- Li, Zhixiong -- Baum, Christopher -- New York, N.Y. -- Science. 2005 May 20;308(5725):1171-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bone Marrow Transplantation, University Hospital Eppendorf, Martinistrasse 52, 20251 Hamburg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15905401" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antigens, CD34/genetics
;
Bone Marrow Transplantation
;
DNA-Binding Proteins/genetics
;
Down-Regulation
;
*Genetic Vectors
;
*Hematopoiesis
;
*Hematopoietic Stem Cell Transplantation
;
Hematopoietic Stem Cells/*physiology
;
Humans
;
Ligase Chain Reaction
;
Mice
;
Mice, Inbred C57BL
;
*Mutagenesis, Insertional
;
Polymerase Chain Reaction
;
Proto-Oncogenes/genetics
;
Retroviridae/*genetics
;
Transcription Factors/genetics
;
Transcription, Genetic
;
Transgenes
;
Up-Regulation
;
*Virus Integration
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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