Delivery and processing of exogenous double-stranded DNA in mouse CD34+ hematopoietic progenitor cells and their cell cycle changes upon combined treatment with cyclophosphamide and double-stranded DNA

Долгова, Е. В.; Efremov, Yaroslav R.; Orishchenko, Кonstantin E.; Andrushkevich, Oleg M.; Alyamkina, E. A.; Proskurina, Anastasia S.; Bayborodin, Sergey I.; Николин, В. П.; Попова, Н. А.; Черных, Е. Р.; Останин, А. А.; Taranov, Oleg S.; Омигов, В. В.; Minkevich, Alexandra M.; Рогачев, В. А.; Богачев, С. С.; Shurdov, Mikhail A.

doi:10.1016/j.gene.2013.06.058

Cited by 33 publications

(38 citation statements)

References 16 publications

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“…7A and B). One percent of mouse bone marrow cells (or 40% of CD34 + cells) are capable of internalizing dsDNA 16 . In humans, 0.25% of bone marrow cells (or 11.7% of CD34 + cells) and 2–5% mesenchymal stem cells show evidence of dsDNA internalization (Fig.…”

Section: Resultsmentioning

confidence: 94%

“…At the same time, we showed that synergistic action of CP and dsDNA may alter hematopoietic stem cells so that some of their pluripotency properties are lost 15 , 16 …”

Section: Resultsmentioning

confidence: 96%

“…Studies of exogenous dsDNA fragment internalization by mouse bone marrow cells reported an interesting fact that up to 40% of hematopoietic CD34 + progenitors can incorporate DNA 15 , 16 . Subsequent analysis suggested that internalization of dsDNA fragments is a general feature of undifferentiated cells with stem cell potential.…”

Section: Resultsmentioning

confidence: 99%

“…These data suggested that presence of dsDNA inside bone marrow cells while they are trying to repair CP-induced ICLs interferes with this repair, resulting in a severely compromised pluripotency of hematopoietic stem cells 15 , 16 . It was suggested that dsDNA fragments internalized into nuclei of tumor-forming cells (in the context of Krebs-2 ascites) may similarly interfere with the repair process.…”

Section: Resultsmentioning

confidence: 99%

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Identification of cancer stem cells and a strategy for their elimination

Долгова

Alyamkina

Efremov

et al. 2014

Cancer Biology & Therapy

100

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It has been established previously that up to 40% of mouse CD34+ hematopoietic stem cells are capable of internalizing exogenous dsDNA fragments both in vivo and ex vivo. Importantly, when mice are treated with a combination of cyclophosphamide and dsDNA, the repair of interstrand crosslinks in hematopoietic progenitors is attenuated, and their pluripotency is altered. Here we show for the first time that among various actively proliferating mammalian cell populations there are subpopulations capable of internalizing dsDNA fragments. In the context of cancer, such dsDNA-internalizing cell subpopulations display cancer stem cell-like phenotype. Furthermore, using Krebs-2 ascites cells as a model, we found that upon combined treatment with cyclophosphamide and dsDNA, engrafted material loses its tumor-initiating properties which we attribute to the elimination of tumor-initiating stem cell subpopulation or loss of its tumorigenic potential.

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Section: Resultsmentioning

confidence: 94%

“…At the same time, we showed that synergistic action of CP and dsDNA may alter hematopoietic stem cells so that some of their pluripotency properties are lost 15 , 16 …”

Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Identification of cancer stem cells and a strategy for their elimination

Долгова

Alyamkina

Efremov

et al. 2014

Cancer Biology & Therapy

100

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“…Primary free-floating spheres were shown to contain cells with the characteristic B cell surface marker CD20. The spheres contained 1-3% of cells with inherent capability of internalizing a TAMRAlabeled double-stranded DNA probe [7][8][9][10][11][12][13][14]. These undifferentiated cells, together with a group of floating TAMRA-negative cells, constituted a sphere-organizing center, inducing repeated aggregation of cells into a spherical 3d structure.…”

mentioning

confidence: 99%

Identification of the xenograft and its ascendant sphere-forming cell line as belonging to EBV-induced lymphoma, and characterization of the status of sphere-forming cells

et al. 2019

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Background: We have characterized the human cell line arised from the Epstein-Barr virus (EBV) positive multiple myeloma aspirate subjected to the long-term cultivation. This cell line has acquired the ability to form free-floating spheres and to produce a xenograft upon transplantation into NOD/SCID mice.Methods: Cells from both in vitro culture and developed xenografts were investigated with a number of analytical approaches, including pathomorphological analysis, FISH analysis, and analysis of the surface antigens and of the VDJ locus rearrangement. Results:The obtained results, as well as the confirmed presence of EBV, testify that both biological systems are derived from B-cells, which, in turn, is a progeny of the EBV-transformed B-cellular clone that supplanted the primordial multiple myeloma cells. Next we assessed whether cells that (i) were constantly present in vitro in the investigated cell line, (ii) were among the sphere-forming cells, and (iii) were capable of internalizing a fluorescent TAMRA-labeled DNA probe (TAMRA+ cells) belonged to one of the three types of undifferentiated bone marrow cells of a multiple myeloma patient: CD34+ hematopoietic stem cells, CD90+ mesenchymal stem cells, and clonotypic multiple myeloma cell.Conclusion: TAMRA+ cells were shown to constitute the fourth independent subpopulation of undifferentiated bone marrow cells of the multiple myeloma patient. We have demonstrated the formation of ectopic contacts between TAMRA+ cells and cells of other types in culture, in particular with CD90+ mesenchymal stem cells, followed by the transfer of some TAMRA+ cell material into the contacted cell.

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