A concept of natural genome reconstruction. Part 2. Effect of extracellular double-stranded DNA fragments on hematopoietic stem cells
In this part of the study, the first component of the concept of “natural genome reconstruction” is being proven. It was shown with mouse and human model organisms that CD34+ hematopoietic bone marrow progenitors take up fragments of extracellular double-stranded DNA through a natural mechanism. It...
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| Format: | Article |
| Language: | English |
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Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
2025-01-01
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| Series: | Вавиловский журнал генетики и селекции |
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| Online Access: | https://vavilov.elpub.ru/jour/article/view/4420 |
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| author | V. S. Ruzanova S. G. Oshikhmina A. S. Proskurina G. S. Ritter S. S. Kirikovich E. V. Levites Y. R. Efremov T. V. Karamysheva M. I. Meschaninova A. L. Mamaev O. S. Taranov A. S. Bogachev S. V. Sidorov S. D. Nikonov O. Y. Leplina A. A. Ostanin E. R. Chernykh N. A. Kolchanov E. V. Dolgova S. S. Bogachev |
| author_facet | V. S. Ruzanova S. G. Oshikhmina A. S. Proskurina G. S. Ritter S. S. Kirikovich E. V. Levites Y. R. Efremov T. V. Karamysheva M. I. Meschaninova A. L. Mamaev O. S. Taranov A. S. Bogachev S. V. Sidorov S. D. Nikonov O. Y. Leplina A. A. Ostanin E. R. Chernykh N. A. Kolchanov E. V. Dolgova S. S. Bogachev |
| author_sort | V. S. Ruzanova |
| collection | DOAJ |
| description | In this part of the study, the first component of the concept of “natural genome reconstruction” is being proven. It was shown with mouse and human model organisms that CD34+ hematopoietic bone marrow progenitors take up fragments of extracellular double-stranded DNA through a natural mechanism. It is known that the process of internalization of extracellular DNA fragments involves glycocalyx structures, which include glycoproteins/protein glycans, glycosylphosphatidylinositol-anchored proteins and scavenger receptors. The bioinformatic analysis conducted indicates that the main surface marker proteins of hematopoietic stem cells belong to the indicated groups of factors and contain specific DNA binding sites, including a heparin-binding domain and clusters of positively charged amino acid residues. A direct interaction of CD34 and CD84 (SLAMF5) glycoproteins, markers of hematopoietic stem cells, with double-stranded DNA fragments was demonstrated using an electrophoretic mobility shift assay system. In cells negative for CD34, which also internalize fragments, concatemerization of the fragments delivered into the cell occurs. In this case, up to five oligonucleotide monomers containing 9 telomeric TTAGGG repeats are stitched together into one structure. Extracellular fragments delivered to hematopoietic stem cells initiate division of the original hematopoietic stem cell in such a way that one of the daughter cells becomes committed to terminal differentiation, and the second retains its low-differentiated status. After treatment of bone marrow cells with hDNAgr, the number of CD34+ cells in the colonies increases to 3 % (humans as the model organism). At the same time, treatment with hDNAgr induces proliferation of blood stem cells and their immediate descendants and stimulates colony formation (mouse, rat and humans as the model organisms). Most often, the granulocyte-macrophage lineage of hematopoiesis is activated as a result of processing extracellular double-stranded DNA. The commitment process is manifested by the appearance and repair of pangenomic single-strand breaks. The transition time in the direction of differentiation (the time it takes for pangenomic single-strand breaks to appear and to be repaired) is about 7 days. It is assumed that at the moment of initiation of pangenomic single-strand breaks, a “recombinogenic situation” ensues in the cell and molecular repair and recombination mechanisms are activated. In all experiments with individual molecules, recombinant human angiogenin was used as a comparison factor. In all other experiments, one of the experimental groups consisted of hematopoietic stem cells treated with angiogenin. |
| format | Article |
| id | doaj-art-7370056b25484a70983e4d049f3deeb3 |
| institution | Kabale University |
| issn | 2500-3259 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders |
| record_format | Article |
| series | Вавиловский журнал генетики и селекции |
| spelling | doaj-art-7370056b25484a70983e4d049f3deeb32025-02-01T09:58:14ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592025-01-01288993100710.18699/vjgb-24-1061533A concept of natural genome reconstruction. Part 2. Effect of extracellular double-stranded DNA fragments on hematopoietic stem cellsV. S. Ruzanova0S. G. Oshikhmina1A. S. Proskurina2G. S. Ritter3S. S. Kirikovich4E. V. Levites5Y. R. Efremov6T. V. Karamysheva7M. I. Meschaninova8A. L. Mamaev9O. S. Taranov10A. S. Bogachev11S. V. Sidorov12S. D. Nikonov13O. Y. Leplina14A. A. Ostanin15E. R. Chernykh16N. A. Kolchanov17E. V. Dolgova18S. S. Bogachev19Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State UniversityInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of SciencesLaboratory Angiopharm LLCState Scientific Center of Virology and Biotechnology “Vector” of RospotrebnadzorNovosibirsk State UniversityCity Clinical Hospital No. 1Novosibirsk Tuberculosis Research InstituteResearch Institute of Fundamental and Clinical ImmunologyResearch Institute of Fundamental and Clinical ImmunologyResearch Institute of Fundamental and Clinical ImmunologyInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesIn this part of the study, the first component of the concept of “natural genome reconstruction” is being proven. It was shown with mouse and human model organisms that CD34+ hematopoietic bone marrow progenitors take up fragments of extracellular double-stranded DNA through a natural mechanism. It is known that the process of internalization of extracellular DNA fragments involves glycocalyx structures, which include glycoproteins/protein glycans, glycosylphosphatidylinositol-anchored proteins and scavenger receptors. The bioinformatic analysis conducted indicates that the main surface marker proteins of hematopoietic stem cells belong to the indicated groups of factors and contain specific DNA binding sites, including a heparin-binding domain and clusters of positively charged amino acid residues. A direct interaction of CD34 and CD84 (SLAMF5) glycoproteins, markers of hematopoietic stem cells, with double-stranded DNA fragments was demonstrated using an electrophoretic mobility shift assay system. In cells negative for CD34, which also internalize fragments, concatemerization of the fragments delivered into the cell occurs. In this case, up to five oligonucleotide monomers containing 9 telomeric TTAGGG repeats are stitched together into one structure. Extracellular fragments delivered to hematopoietic stem cells initiate division of the original hematopoietic stem cell in such a way that one of the daughter cells becomes committed to terminal differentiation, and the second retains its low-differentiated status. After treatment of bone marrow cells with hDNAgr, the number of CD34+ cells in the colonies increases to 3 % (humans as the model organism). At the same time, treatment with hDNAgr induces proliferation of blood stem cells and their immediate descendants and stimulates colony formation (mouse, rat and humans as the model organisms). Most often, the granulocyte-macrophage lineage of hematopoiesis is activated as a result of processing extracellular double-stranded DNA. The commitment process is manifested by the appearance and repair of pangenomic single-strand breaks. The transition time in the direction of differentiation (the time it takes for pangenomic single-strand breaks to appear and to be repaired) is about 7 days. It is assumed that at the moment of initiation of pangenomic single-strand breaks, a “recombinogenic situation” ensues in the cell and molecular repair and recombination mechanisms are activated. In all experiments with individual molecules, recombinant human angiogenin was used as a comparison factor. In all other experiments, one of the experimental groups consisted of hematopoietic stem cells treated with angiogenin.https://vavilov.elpub.ru/jour/article/view/4420hematopoietic stem cellsextracellular dnainternalizationterminal differentiationsingle-strand breaks |
| spellingShingle | V. S. Ruzanova S. G. Oshikhmina A. S. Proskurina G. S. Ritter S. S. Kirikovich E. V. Levites Y. R. Efremov T. V. Karamysheva M. I. Meschaninova A. L. Mamaev O. S. Taranov A. S. Bogachev S. V. Sidorov S. D. Nikonov O. Y. Leplina A. A. Ostanin E. R. Chernykh N. A. Kolchanov E. V. Dolgova S. S. Bogachev A concept of natural genome reconstruction. Part 2. Effect of extracellular double-stranded DNA fragments on hematopoietic stem cells Вавиловский журнал генетики и селекции hematopoietic stem cells extracellular dna internalization terminal differentiation single-strand breaks |
| title | A concept of natural genome reconstruction. Part 2. Effect of extracellular double-stranded DNA fragments on hematopoietic stem cells |
| title_full | A concept of natural genome reconstruction. Part 2. Effect of extracellular double-stranded DNA fragments on hematopoietic stem cells |
| title_fullStr | A concept of natural genome reconstruction. Part 2. Effect of extracellular double-stranded DNA fragments on hematopoietic stem cells |
| title_full_unstemmed | A concept of natural genome reconstruction. Part 2. Effect of extracellular double-stranded DNA fragments on hematopoietic stem cells |
| title_short | A concept of natural genome reconstruction. Part 2. Effect of extracellular double-stranded DNA fragments on hematopoietic stem cells |
| title_sort | concept of natural genome reconstruction part 2 effect of extracellular double stranded dna fragments on hematopoietic stem cells |
| topic | hematopoietic stem cells extracellular dna internalization terminal differentiation single-strand breaks |
| url | https://vavilov.elpub.ru/jour/article/view/4420 |
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