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Introduction of a selectable gene into primitive stem cells capable of long-term reconstitution of the hemopoietic system of W/W mice
Abstract
We have used the random chromosomal integration sites of retrovirus vectors as unique clonal markers to analyze cell lineage relationships within the hemopoietic stem cell hierarchy. Using a high efficiency protocol for retrovirus-mediated gene transfer, anemic W/Wv mutant mice were reconstituted with bone marrow cells infected with a NEO vector. Analysis of the DNA from bone marrow, thymus, and spleen of these reconstituted W/Wv mice indicated insertion of the vector into primitive pluripotent stem cells capable of producing both myeloid and lymphoid progeny as well as into more committed stem cells apparently restricted to either the myeloid or lymphoid lineages. The neo gene was also expressed in these mice, as they contained a variety of G418 resistant in vitro colony-forming cells. These results demonstrate high-efficiency gene transfer and expression in primitive hemopoietic stem cells and provide a direct approach for analyzing the hemopoietic stem cell hierarchy.
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“Thus, the major breakthrough in the field was adoption of γ-retroviruses as vectors to transfer DNA into HSPCs (Figure 1).4,5”
From Ex vivo modification of hematopoietic stem and progenitor cells for gene therapy (2025) · cites this paper as [5]
In the citing paper
“Our high-resolution fate mapping experiments of embryonic HSC progenitors and adult HSC both support a bifurcating tree model of hematopoiesis, which was proposed in the 1980s24, but has not been tested under physiological conditions.”
From Polylox barcoding reveals haematopoietic stem cell fates realized in vivo (2017) · cites this paper as [24]
Citations
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Van Zant, G., Holland, B. P., Eldridge, P. W., & Chen, J. J. (1990) · The Journal of Experimental Medicine · doi:10.1084/jem.171.5.1547 · Cited by 99
The impact of aging on primate hematopoiesis as interrogated by clonal tracking
Yu, K.-R., Espinoza, D. A., Wu, C., Truitt, L., Shin, T.-H., Chen, S., Fan, X., Yabe, I. M., Panch, S., Hong, S. G., et al. (2018) · Blood · doi:10.1182/blood-2017-08-802033 · Cited by 47
Ex vivo modification of hematopoietic stem and progenitor cells for gene therapy
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Faltusová, K., Szikszai, K., Molík, M., Linhartová, J., Páral, P., Šefc, L., Savvulidi, F., & Nečas, E. (2018) · Stem Cells · doi:10.1002/stem.2828 · Cited by 8
Metadata
- Authors
- Dick, J. E., Magli, M. C., Huszar, D., Phillips, R. A., & Bernstein, A.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1985-08
- Volume
- 42
- Issue
- 1
- Pages
- 71-79
- ISSN
- 0092-8674
- Cited by
- 446
- References
- 1
- Language
- en
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