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Persisting multilineage transgene expression in the clonal progeny of a hematopoietic stem cell

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Persisting multilineage transgene expression in the clonal progeny of a hematopoietic stem cell. / Li, Z; Fehse, B; Schiedlmeier, B; Düllmann, J; Frank, O; Zander, A R; Ostertag, W; Baum, C.

In: LEUKEMIA, Vol. 16, No. 9, 09.2002, p. 1655-63.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Li, Z, Fehse, B, Schiedlmeier, B, Düllmann, J, Frank, O, Zander, AR, Ostertag, W & Baum, C 2002, 'Persisting multilineage transgene expression in the clonal progeny of a hematopoietic stem cell', LEUKEMIA, vol. 16, no. 9, pp. 1655-63. https://doi.org/10.1038/sj.leu.2402619

APA

Li, Z., Fehse, B., Schiedlmeier, B., Düllmann, J., Frank, O., Zander, A. R., Ostertag, W., & Baum, C. (2002). Persisting multilineage transgene expression in the clonal progeny of a hematopoietic stem cell. LEUKEMIA, 16(9), 1655-63. https://doi.org/10.1038/sj.leu.2402619

Vancouver

Li Z, Fehse B, Schiedlmeier B, Düllmann J, Frank O, Zander AR et al. Persisting multilineage transgene expression in the clonal progeny of a hematopoietic stem cell. LEUKEMIA. 2002 Sep;16(9):1655-63. https://doi.org/10.1038/sj.leu.2402619

Bibtex

@article{52b6cb4bb5b14b3da2ceb7cd8b7f1b39,
title = "Persisting multilineage transgene expression in the clonal progeny of a hematopoietic stem cell",
abstract = "Many applications of hematopoietic gene therapy require selection for clones with active transgene expression. However, it was unclear whether the clonal progeny of a retrovirally transduced hematopoietic stem cell would be capable of maintaining transgene expression through serial repopulation and multilineage differentiation. Such investigations require simultaneous analyses of clonality, multilineage activity and transgene copy numbers. Using a mouse model, the present study demonstrates that a single hematopoietic stem cell expressing a marker gene from one or two insertions of a simple retroviral vector actively maintains multilineage transgene expression in the vast majority (80-99%) of bone marrow and peripheral blood cells. Gene expression persisted through serial transplantations for at least 97 weeks post gene transfer and was observed in the lymphoid (B, T and NK cells), myeloid (CD11b(+), Gr-1(+)), erythroid (Ter119(+), mature red blood cells) and megakaryocytic (as indicated by platelets) progeny. Therefore, a single immunoselection for hematopoietic stem cells expressing the transgene in vivo was sufficient to establish a completely chimeric hematopoiesis. These observations imply that the retroviral vectors used in this study contain cis-elements that mediate expression through massive clonal expansion and multilineage differentiation, provided the insertion occurred in genetic loci permissive for expression in hematopoietic stem cells.",
keywords = "Animals, Antigens, CD34/genetics, Bone Marrow Cells/metabolism, Cell Lineage/physiology, Chimera, Colony-Forming Units Assay, Female, Gene Dosage, Gene Silencing, Gene Transfer Techniques, Green Fluorescent Proteins, Hematopoiesis/physiology, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells/physiology, Humans, Luminescent Proteins/metabolism, Mice, Mice, Inbred C57BL, Mice, Transgenic, Retroviridae/genetics, Transduction, Genetic, Transfection, Transgenes/physiology",
author = "Z Li and B Fehse and B Schiedlmeier and J D{\"u}llmann and O Frank and Zander, {A R} and W Ostertag and C Baum",
year = "2002",
month = sep,
doi = "10.1038/sj.leu.2402619",
language = "English",
volume = "16",
pages = "1655--63",
journal = "LEUKEMIA",
issn = "0887-6924",
publisher = "NATURE PUBLISHING GROUP",
number = "9",

}

RIS

TY - JOUR

T1 - Persisting multilineage transgene expression in the clonal progeny of a hematopoietic stem cell

AU - Li, Z

AU - Fehse, B

AU - Schiedlmeier, B

AU - Düllmann, J

AU - Frank, O

AU - Zander, A R

AU - Ostertag, W

AU - Baum, C

PY - 2002/9

Y1 - 2002/9

N2 - Many applications of hematopoietic gene therapy require selection for clones with active transgene expression. However, it was unclear whether the clonal progeny of a retrovirally transduced hematopoietic stem cell would be capable of maintaining transgene expression through serial repopulation and multilineage differentiation. Such investigations require simultaneous analyses of clonality, multilineage activity and transgene copy numbers. Using a mouse model, the present study demonstrates that a single hematopoietic stem cell expressing a marker gene from one or two insertions of a simple retroviral vector actively maintains multilineage transgene expression in the vast majority (80-99%) of bone marrow and peripheral blood cells. Gene expression persisted through serial transplantations for at least 97 weeks post gene transfer and was observed in the lymphoid (B, T and NK cells), myeloid (CD11b(+), Gr-1(+)), erythroid (Ter119(+), mature red blood cells) and megakaryocytic (as indicated by platelets) progeny. Therefore, a single immunoselection for hematopoietic stem cells expressing the transgene in vivo was sufficient to establish a completely chimeric hematopoiesis. These observations imply that the retroviral vectors used in this study contain cis-elements that mediate expression through massive clonal expansion and multilineage differentiation, provided the insertion occurred in genetic loci permissive for expression in hematopoietic stem cells.

AB - Many applications of hematopoietic gene therapy require selection for clones with active transgene expression. However, it was unclear whether the clonal progeny of a retrovirally transduced hematopoietic stem cell would be capable of maintaining transgene expression through serial repopulation and multilineage differentiation. Such investigations require simultaneous analyses of clonality, multilineage activity and transgene copy numbers. Using a mouse model, the present study demonstrates that a single hematopoietic stem cell expressing a marker gene from one or two insertions of a simple retroviral vector actively maintains multilineage transgene expression in the vast majority (80-99%) of bone marrow and peripheral blood cells. Gene expression persisted through serial transplantations for at least 97 weeks post gene transfer and was observed in the lymphoid (B, T and NK cells), myeloid (CD11b(+), Gr-1(+)), erythroid (Ter119(+), mature red blood cells) and megakaryocytic (as indicated by platelets) progeny. Therefore, a single immunoselection for hematopoietic stem cells expressing the transgene in vivo was sufficient to establish a completely chimeric hematopoiesis. These observations imply that the retroviral vectors used in this study contain cis-elements that mediate expression through massive clonal expansion and multilineage differentiation, provided the insertion occurred in genetic loci permissive for expression in hematopoietic stem cells.

KW - Animals

KW - Antigens, CD34/genetics

KW - Bone Marrow Cells/metabolism

KW - Cell Lineage/physiology

KW - Chimera

KW - Colony-Forming Units Assay

KW - Female

KW - Gene Dosage

KW - Gene Silencing

KW - Gene Transfer Techniques

KW - Green Fluorescent Proteins

KW - Hematopoiesis/physiology

KW - Hematopoietic Stem Cell Transplantation

KW - Hematopoietic Stem Cells/physiology

KW - Humans

KW - Luminescent Proteins/metabolism

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Retroviridae/genetics

KW - Transduction, Genetic

KW - Transfection

KW - Transgenes/physiology

U2 - 10.1038/sj.leu.2402619

DO - 10.1038/sj.leu.2402619

M3 - SCORING: Journal article

C2 - 12200677

VL - 16

SP - 1655

EP - 1663

JO - LEUKEMIA

JF - LEUKEMIA

SN - 0887-6924

IS - 9

ER -