Clonal dominance of hematopoietic stem cells triggered by retroviral gene marking
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Clonal dominance of hematopoietic stem cells triggered by retroviral gene marking. / Kustikova, Olga; Fehse, Boris; Modlich, Ute; Yang, Min; Düllmann, Jochen; Kamino, Kenji; von Neuhoff, Nils; Schlegelberger, Brigitte; Li, Zhixiong; Baum, Christopher.
In: SCIENCE, Vol. 308, No. 5725, 20.05.2005, p. 1171-4.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Clonal dominance of hematopoietic stem cells triggered by retroviral gene marking
AU - Kustikova, Olga
AU - Fehse, Boris
AU - Modlich, Ute
AU - Yang, Min
AU - Düllmann, Jochen
AU - Kamino, Kenji
AU - von Neuhoff, Nils
AU - Schlegelberger, Brigitte
AU - Li, Zhixiong
AU - Baum, Christopher
PY - 2005/5/20
Y1 - 2005/5/20
N2 - 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.
AB - 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.
KW - Animals
KW - Antigens, CD34/genetics
KW - Bone Marrow Transplantation
KW - DNA-Binding Proteins/genetics
KW - Down-Regulation
KW - Genetic Vectors
KW - Hematopoiesis
KW - Hematopoietic Stem Cell Transplantation
KW - Hematopoietic Stem Cells/physiology
KW - Humans
KW - Ligase Chain Reaction
KW - MDS1 and EVI1 Complex Locus Protein
KW - Mice
KW - Mice, Inbred C57BL
KW - Mutagenesis, Insertional
KW - Polymerase Chain Reaction
KW - Proto-Oncogenes/genetics
KW - Retroviridae/genetics
KW - Transcription Factors/genetics
KW - Transcription, Genetic
KW - Transgenes
KW - Up-Regulation
KW - Virus Integration
U2 - 10.1126/science.1105063
DO - 10.1126/science.1105063
M3 - SCORING: Journal article
C2 - 15905401
VL - 308
SP - 1171
EP - 1174
JO - SCIENCE
JF - SCIENCE
SN - 0036-8075
IS - 5725
ER -