vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/vjgb-24-106vavilov-4420Research ArticleБИОМЕДИЦИНАBIOMEDICINEКонцепция природной реконструкции генома. Часть 2. Влияние фрагментов экстраклеточной двуцепочечной ДНК на гемопоэтические стволовые клеткиA concept of natural genome reconstruction. Part 2. Effect of extracellular double-stranded DNA fragments on hematopoietic stem cellshttps://orcid.org/0000-0002-6836-5618РузановаВ. С.RuzanovaV. S.

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Novosibirsk

https://orcid.org/0009-0002-6432-1762ОшихминаС. Г.OshikhminaS. G.

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Novosibirsk

https://orcid.org/0000-0002-7650-4331ПроскуринаА. С.ProskurinaA. S.

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Novosibirsk

https://orcid.org/0000-0003-1573-3795РиттерГ. С.RitterG. S.

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Novosibirsk

https://orcid.org/0000-0002-3426-4501КириковичС. С.KirikovichS. S.

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Novosibirsk

https://orcid.org/0000-0002-3093-407XЛевитесЕ. В.LevitesE. V.

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Novosibirsk

https://orcid.org/0000-0002-0649-7543ЕфремовЯ. Р.EfremovY. R.

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Novosibirsk

КарамышеваТ. В.KaramyshevaT. V.

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Novosibirsk

https://orcid.org/0000-0003-0045-2413МещаниноваМ. И.MeschaninovaM. I.

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Novosibirsk

МамаевА. Л.MamaevA. L.

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Novosibirsk

https://orcid.org/0000-0002-6746-8092ТарановО. С.TaranovO. S.

р. п. Кольцово, Новосибирская область

Koltsovo, Novosibirsk region

БогачевА. С.BogachevA. S.

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Novosibirsk

СидоровС. В.SidorovS. V.

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Novosibirsk

НиконовС. Д.NikonovS. D.

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Novosibirsk

https://orcid.org/0000-0003-3169-8643ЛеплинаО. Ю.LeplinaO. Y.

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Novosibirsk

https://orcid.org/0000-0001-6895-938XОстанинА. А.OstaninA. A.

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Novosibirsk

https://orcid.org/0000-0003-2346-6279ЧерныхЕ. Р.ChernykhE. R.

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Novosibirsk

https://orcid.org/0000-0001-6800-8787КолчановН. А.KolchanovN. A.

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Novosibirsk

https://orcid.org/0000-0002-5543-248XДолговаЕ. В.DolgovaE. V.

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Novosibirsk

https://orcid.org/0000-0002-2019-9382БогачевС. С.BogachevS. S.

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Novosibirsk

labmolbiol@mail.ruИнститут химической биологии и фундаментальной медицины Сибирского отделения Российской академии наукРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesRussian FederationИнститут химической биологии и фундаментальной медицины Сибирского отделения Российской академии наук; Новосибирский национальный исследовательский государственный университетРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State UniversityRussian FederationИнститут химической биологии и фундаментальной медицины Сибирского отделения Российской академии наукРоссияInstitute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of SciencesRussian FederationООО «Лаборатория Ангиофарм»РоссияLaboratory Angiopharm LLCRussian FederationГосударственный научный центр вирусологии и биотехнологии «Вектор» РоспотребнадзораРоссияState Scientific Center of Virology and Biotechnology “Vector” of RospotrebnadzorRussian FederationНовосибирский национальный исследовательский государственный университетРоссияNovosibirsk State UniversityRussian FederationГородская клиническая больница № 1РоссияCity Clinical Hospital No. 1Russian FederationНовосибирский научно-исследовательский институт туберкулезаРоссияNovosibirsk Tuberculosis Research InstituteRussian FederationНаучно-исследовательский институт фундаментальной и клинической иммунологииРоссияResearch Institute of Fundamental and Clinical ImmunologyRussian FederationФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наукРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesRussian Federation2024260120252889931007Copyright © Рузанова В.С., Ошихмина С.Г., Проскурина А.С., Риттер Г.С., Кирикович С.С., Левитес Е.В., Ефремов Я.Р., Карамышева Т.В., Мещанинова М.И., Мамаев А.Л., Таранов О.С., Богачев А.С., Сидоров С.В., Никонов С.Д., Леплина О.Ю., Останин А.А., Черных Е.Р., Колчанов Н.А., Долгова Е.В., Богачев С.С., 20252025Рузанова В.С., Ошихмина С.Г., Проскурина А.С., Риттер Г.С., Кирикович С.С., Левитес Е.В., Ефремов Я.Р., Карамышева Т.В., Мещанинова М.И., Мамаев А.Л., Таранов О.С., Богачев А.С., Сидоров С.В., Никонов С.Д., Леплина О.Ю., Останин А.А., Черных Е.Р., Колчанов Н.А., Долгова Е.В., Богачев С.С.Ruzanova V.S., Oshikhmina S.G., Proskurina A.S., Ritter G.S., Kirikovich S.S., Levites E.V., Efremov Y.R., Karamysheva T.V., Meschaninova M.I., Mamaev A.L., Taranov O.S., Bogachev A.S., Sidorov S.V., Nikonov S.D., Leplina O.Y., Ostanin A.A., Chernykh E.R., Kolchanov N.A., Dolgova E.V., Bogachev S.S.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/4420

В настоящей части исследования доказывается первая составляющая концепции «природной реконструкции генома». На модельных организмах мышь и человек показано, что CD34+ гемопоэтические предшественники костного мозга захватывают фрагменты экстраклеточной двуцепочечной ДНК естественным природным механизмом. Известно, что в процессе интернализации экстраклеточных фрагментов ДНК принимают участие структуры гликокаликса, в состав которых входят гликопротеины/протеогликаны, гликозилфосфатидилинозитол-заякоренные белки и скавенджер-рецепторы. Проведенный биоинформационный анализ свидетельствует, что основные поверхностные маркерные белки гемопоэтических стволовых клеток относятся к указанным группам факторов и содержат специфические сайты связывания ДНК, включающие гепарин-связывающий домен и кластеры положительно заряженных аминокислотных остатков. С использованием системы Electrophoretic mobility shift assay показано прямое взаимодействие CD34 и CD84 (SLAMF5) гликопротеинов, маркеров гемопоэтических стволовых клеток, с фрагментами двуцепочечной ДНК. В клетках, негативных по CD34, также интернализующих фрагменты, происходит конкатемеризация доставленных внутрь клетки фрагментов. При этом в одну структуру сшивается до пяти мономеров олигонуклеотидов, содержащих девять теломерных повторов TTAGGG. Доставленные в гемопоэтические стволовые клетки экстраклеточные фрагменты инициируют деление исходной гемопоэтической стволовой клетки таким образом, что одна из дочерних клеток уходит в терминальную дифференцировку, а вторая сохраняет свой низкодифференцированный статус. В составе колоний после обработки клеток костного мозга препаратом hDNAgr количество СD34+ клеток возрастает до 3 % (модельный организм – человек). Одновременно обработка препаратом hDNAgr индуцирует пролиферацию стволовых клеток крови и их ближайших потомков и стимулирует колониеобразование (модельные организмы – мышь, крыса, человек). Наиболее часто в результате обработки экстраклеточной двуцепочечной ДНК активируется гранулоцитарно-макрофагальный росток кроветворения. Процесс коммитирования манифестируется появлением и репарацией пангеномных одноцепочечных разрывов. Время перехода в направлении дифференцировки (время появления и репарации пангеномных одноцепочечных разрывов) составляет около 7 суток. Предполагается, что в момент инициации пангеномных одноцепочечных разрывов в клетке создается «рекомбиногенная ситуация» и активируются молекулярные репаративно-рекомбинационные механизмы. Во всех проведенных экспериментах по анализу индивидуальных молекул в качестве фактора сравнения использовался ангиогенин рекомбинантный человеческий. Во всех других экспериментах одной из сравниваемых групп являлись гемопоэтические стволовые клетки, обработанные ангиогенином.

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.

гемопоэтические стволовые клеткиэкстраклеточная ДНКинтернализациятерминальная дифференцировкаодноцепочечные разрывыhematopoietic stem cellsextracellular DNAinternalizationterminal differentiationsingle-strand breaksThis work was supported by the Ministry of Science and Higher Education of the Russian Federation for the Institute of Cytology and Genetics (state budget-funded project No. FWNR-2022-0016) and by LLC “ES.LAB DIAGNOSTIC”, I.N. Zaitseva and A.A. Purtov.ReferencesBoerrigter M.E.T.I., Mullaart E., Van Der Schans G.P., Vijg J. Quiescent human peripheral blood lymphocytes do not contain a sizable amount of preexistent DNA single-strand breaks. Exp. Cell Res. 1989;180(2):569-573. doi 10.1016/0014-4827(89)90085-2Boerrigter M.E.T.I., Mullaart E., Van Der Schans G.P., Vijg J. Quiescent human peripheral blood lymphocytes do not contain a sizable amount of preexistent DNA single-strand breaks. Exp. Cell Res. 1989;180(2):569-573. doi 10.1016/0014-4827(89)90085-2Chen J.M., Cooper D.N., Chuzhanova N., Férec C., Patrinos G.P. Gene conversion: mechanisms, evolution and human disease. Nat. Rev. Genet. 2007;8(10):762-775. doi 10.1038/NRG2193Chen J.M., Cooper D.N., Chuzhanova N., Férec C., Patrinos G.P. Gene conversion: mechanisms, evolution and human disease. Nat. Rev. Genet. 2007;8(10):762-775. doi 10.1038/NRG2193Chen T.L., Chiang Y.W., Lin G.L., Chang H.H., Lien T.S., Sheh M.H., Sun D.S. Different effects of granulocyte colony-stimulating factor and erythropoietin on erythropoiesis. Stem. Cell Res. Ther. 2018; 9(1):119. doi 10.1186/S13287-018-0877-2Chen T.L., Chiang Y.W., Lin G.L., Chang H.H., Lien T.S., Sheh M.H., Sun D.S. Different effects of granulocyte colony-stimulating factor and erythropoietin on erythropoiesis. Stem. Cell Res. Ther. 2018; 9(1):119. doi 10.1186/S13287-018-0877-2Desterke C., Bennaceur-Griscelli A., Turhan A.G. EGR1 dysregulation defines an inflammatory and leukemic program in cell trajectory of human-aged hematopoietic stem cells (HSC). Stem. Cell Res. Ther. 2021;12(1):419. doi 10.1186/S13287-021-02498-0Desterke C., Bennaceur-Griscelli A., Turhan A.G. EGR1 dysregulation defines an inflammatory and leukemic program in cell trajectory of human-aged hematopoietic stem cells (HSC). Stem. Cell Res. Ther. 2021;12(1):419. doi 10.1186/S13287-021-02498-0DNA Cloning. A practical approach. Ed. D.M. Glover. IRL Press, 1985DNA Cloning. A practical approach. Ed. D.M. Glover. IRL Press, 1985Dolgova E.V., Efremov Y.R., Orishchenko K.E., Andrushkevich O.M., Alyamkina E.A., Proskurina A.S., Bayborodin S.I., Nikolin V.P., Popova N.A., Chernykh E.R., Ostanin A.A., Taranov O.S., Omigov V.V., Minkevich A.M., Rogachev V.A., Bogachev S.S., Shurdov M.A. 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. Gene. 2013;528(2):74-83. doi 10.1016/j.gene.2013.06.058Dolgova E.V., Efremov Y.R., Orishchenko K.E., Andrushkevich O.M., Alyamkina E.A., Proskurina A.S., Bayborodin S.I., Nikolin V.P., Popova N.A., Chernykh E.R., Ostanin A.A., Taranov O.S., Omigov V.V., Minkevich A.M., Rogachev V.A., Bogachev S.S., Shurdov M.A. 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. Gene. 2013;528(2):74-83. doi 10.1016/j.gene.2013.06.058Dolgova E.V., Alyamkina E.A., Efremov Y.R., Nikolin V.P., Popova N.A., Tyrinova T.V., Kozel A.V., Minkevich A.M., Andrushkevich O.M., Zavyalov E.L., Romaschenko A.V., Bayborodin S.I., Taranov O.S., Omigov V.V., Shevela E.Y., Stupak V.V., Mishinov S.V., Rogachev V.A., Proskurina A.S., Mayorov V.I., Shurdov M.A., Ostanin A.A., Chernykh E.R., Bogachev S.S. Identification of cancer stem cells and a strategy for their elimination. Cancer Biol. Ther. 2014;15(10):1378-1394. doi 10.4161/cbt.29854Dolgova E.V., Alyamkina E.A., Efremov Y.R., Nikolin V.P., Popova N.A., Tyrinova T.V., Kozel A.V., Minkevich A.M., Andrushkevich O.M., Zavyalov E.L., Romaschenko A.V., Bayborodin S.I., Taranov O.S., Omigov V.V., Shevela E.Y., Stupak V.V., Mishinov S.V., Rogachev V.A., Proskurina A.S., Mayorov V.I., Shurdov M.A., Ostanin A.A., Chernykh E.R., Bogachev S.S. Identification of cancer stem cells and a strategy for their elimination. Cancer Biol. Ther. 2014;15(10):1378-1394. doi 10.4161/cbt.29854Dolgova E.V., Potter E.A., Proskurina A.S., Minkevich A.M., Chernych E.R., Ostanin A.A., Efremov Y.R., Bayborodin S.I., Nikolin V.P., Popova N.A., Kolchanov N.A., Bogachev S.S. Properties of internalization factors contributing to the uptake of extracellular DNA into tumor-initiating stem cells of mouse Krebs-2 cell line. Stem. Cell Res. Ther. 2016;7(1):76. doi 10.1186/s13287-016-0338-8Dolgova E.V., Potter E.A., Proskurina A.S., Minkevich A.M., Chernych E.R., Ostanin A.A., Efremov Y.R., Bayborodin S.I., Nikolin V.P., Popova N.A., Kolchanov N.A., Bogachev S.S. Properties of internalization factors contributing to the uptake of extracellular DNA into tumor-initiating stem cells of mouse Krebs-2 cell line. Stem. Cell Res. Ther. 2016;7(1):76. doi 10.1186/s13287-016-0338-8Dolgova E.V., Petrova D.D., Proskurina A.S., Ritter G.S., Kisaretova P.E., Potter E.A., Efremov Y.R., Bayborodin S.I., Karamysheva T.V., Romanenko M.V., Netesov S.V., Taranov O.S., Ostanin A.A., Chernykh E.R., Bogachev S.S. 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. Cancer Cell Int. 2019;19:120. doi 10.1186/S12935-019-0842-XDolgova E.V., Petrova D.D., Proskurina A.S., Ritter G.S., Kisaretova P.E., Potter E.A., Efremov Y.R., Bayborodin S.I., Karamysheva T.V., Romanenko M.V., Netesov S.V., Taranov O.S., Ostanin A.A., Chernykh E.R., Bogachev S.S. 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. Cancer Cell Int. 2019;19:120. doi 10.1186/S12935-019-0842-XFarzaneh F., Zalin R., Brill D., Shall S. DNA strand breaks and ADPribosyl transferase activation during cell differentiation. Nature. 1982;300(5890):362-366. doi 10.1038/300362A0Farzaneh F., Zalin R., Brill D., Shall S. DNA strand breaks and ADPribosyl transferase activation during cell differentiation. Nature. 1982;300(5890):362-366. doi 10.1038/300362A0Forristal C.E., Levesque J.-P. Targeting the hypoxia-sensing pathway in clinical hematology. Stem Cells Transl. Med. 2014;3(2):135-140. doi 10.5966/SCTM.2013-0134Forristal C.E., Levesque J.-P. Targeting the hypoxia-sensing pathway in clinical hematology. Stem Cells Transl. Med. 2014;3(2):135-140. doi 10.5966/SCTM.2013-0134Goncalves K.A., Silberstein L., Li S., Severe N., Hu M.G., Yang H., Scadden D.T., Hu G.F. Angiogenin promotes hematopoietic regeneration by dichotomously regulating quiescence of stem and progenitor cells. Cell. 2016;166(4):894-906. doi 10.1016/J.CELL.2016.06.042Goncalves K.A., Silberstein L., Li S., Severe N., Hu M.G., Yang H., Scadden D.T., Hu G.F. Angiogenin promotes hematopoietic regeneration by dichotomously regulating quiescence of stem and progenitor cells. Cell. 2016;166(4):894-906. doi 10.1016/J.CELL.2016.06.042Hastings P.J., McGill C., Shafer B., Strathern J.N. Ends-in vs. endsout recombination in yeast. Genetics. 1993;135(4):973-980. doi 10.1093/GENETICS/135.4.973Hastings P.J., McGill C., Shafer B., Strathern J.N. Ends-in vs. endsout recombination in yeast. Genetics. 1993;135(4):973-980. doi 10.1093/GENETICS/135.4.973Iseki S. DNA strand breaks in rat tissues as detected by in situ nick translation. Exp. Cell Res. 1986;167(2):311-326. doi 10.1016/0014-4827(86)90172-2Iseki S. DNA strand breaks in rat tissues as detected by in situ nick translation. Exp. Cell Res. 1986;167(2):311-326. doi 10.1016/0014-4827(86)90172-2Jacobson G.K., Pinon R., Esposito R.E., Esposito M.S. Single-strand scissions of chromosomal DNA during commitment to recombination at meiosis. Proc. Natl. Acad. Sci. USA. 1975;72(5):1887-1891. doi 10.1073/PNAS.72.5.1887Jacobson G.K., Pinon R., Esposito R.E., Esposito M.S. Single-strand scissions of chromosomal DNA during commitment to recombination at meiosis. Proc. Natl. Acad. Sci. USA. 1975;72(5):1887-1891. doi 10.1073/PNAS.72.5.1887Jiang N., Pisetsky D.S. The effect of inflammation on the generation of plasma DNA from dead and dying cells in the peritoneum. J. Leukoc. Biol. 2005;77(3):296-302. doi 10.1189/JLB.0704411Jiang N., Pisetsky D.S. The effect of inflammation on the generation of plasma DNA from dead and dying cells in the peritoneum. J. Leukoc. Biol. 2005;77(3):296-302. doi 10.1189/JLB.0704411Johnstone A.P., Williams G.T. Role of DNA breaks and ADP-ribosyl transferase activity in eukaryotic differentiation demonstrated in human lymphocytes. Nature. 1982;300(5890):368-370. doi 10.1038/300368A0Johnstone A.P., Williams G.T. Role of DNA breaks and ADP-ribosyl transferase activity in eukaryotic differentiation demonstrated in human lymphocytes. Nature. 1982;300(5890):368-370. doi 10.1038/300368A0Kaminskas E., Li J.C. DNA fragmentation in permeabilized cells and nuclei. The role of (Ca2+ + Mg2+)-dependent endodeoxyribonuclease. Biochem. J. 1989;261(1):17-21. doi 10.1042/BJ2610017Kaminskas E., Li J.C. DNA fragmentation in permeabilized cells and nuclei. The role of (Ca2+ + Mg2+)-dependent endodeoxyribonuclease. Biochem. J. 1989;261(1):17-21. doi 10.1042/BJ2610017Kananen L., Hurme M., Bürkle A., Moreno-Villanueva M., Bernhardt J., Debacq-Chainiaux F., Grubeck-Loebenstein B., Malavolta M., Basso A., Piacenza F., Collino S., Gonos E.S., Sikora E., Gradinaru D., Jansen E.H.J.M., Dollé M.E.T., Salmon M., Stuetz W., Weber D., Grune T., Breusing N., Simm A., Capri M., Franceschi C., Slagboom E., Talbot D., Libert C., Raitanen J., Koskinen S., Härkänen T., Stenholm S., Ala-Korpela M., Lehtimäki T., Raitakari O.T., Ukkola O., Kähönen M., Jylhä M., Jylhävä J. Circulating cell-free DNA in health and disease – the relationship to health behaviours, ageing phenotypes and metabolomics. GeroScience. 2023;45(1): 85-103. doi 10.1007/S11357-022-00590-8Kananen L., Hurme M., Bürkle A., Moreno-Villanueva M., Bernhardt J., Debacq-Chainiaux F., Grubeck-Loebenstein B., Malavolta M., Basso A., Piacenza F., Collino S., Gonos E.S., Sikora E., Gradinaru D., Jansen E.H.J.M., Dollé M.E.T., Salmon M., Stuetz W., Weber D., Grune T., Breusing N., Simm A., Capri M., Franceschi C., Slagboom E., Talbot D., Libert C., Raitanen J., Koskinen S., Härkänen T., Stenholm S., Ala-Korpela M., Lehtimäki T., Raitakari O.T., Ukkola O., Kähönen M., Jylhä M., Jylhävä J. Circulating cell-free DNA in health and disease – the relationship to health behaviours, ageing phenotypes and metabolomics. GeroScience. 2023;45(1): 85-103. doi 10.1007/S11357-022-00590-8Kiang J.G., Zhai M., Lin B., Smith J.T., Anderson M.N., Jiang S. Cotherapy of pegylated G-CSF and ghrelin for enhancing survival after exposure to lethal radiation. Front. Pharmacol. 2021;12: 628018. doi 10.3389/FPHAR.2021.628018Kiang J.G., Zhai M., Lin B., Smith J.T., Anderson M.N., Jiang S. Cotherapy of pegylated G-CSF and ghrelin for enhancing survival after exposure to lethal radiation. Front. Pharmacol. 2021;12: 628018. doi 10.3389/FPHAR.2021.628018Korabecna M., Zinkova A., Brynychova I., Chylikova B., Prikryl P., Sedova L., Neuzil P., Seda O. Cell-free DNA in plasma as an essential immune system regulator. Sci. Rep. 2020;10(1):17478. doi 10.1038/S41598-020-74288-2Korabecna M., Zinkova A., Brynychova I., Chylikova B., Prikryl P., Sedova L., Neuzil P., Seda O. Cell-free DNA in plasma as an essential immune system regulator. Sci. Rep. 2020;10(1):17478. doi 10.1038/S41598-020-74288-2Kovtonyuk L.V., Fritsch K., Feng X., Manz M.G., Takizawa H. Inflamm- aging of hematopoiesis, hematopoietic stem cells, and the bone marrow microenvironment. Front. Immunol. 2016;7:502. doi 10.3389/FIMMU.2016.00502Kovtonyuk L.V., Fritsch K., Feng X., Manz M.G., Takizawa H. Inflamm- aging of hematopoiesis, hematopoietic stem cells, and the bone marrow microenvironment. Front. Immunol. 2016;7:502. doi 10.3389/FIMMU.2016.00502Kulkarni R., Kale V. Physiological cues involved in the regulation of adhesion mechanisms in hematopoietic stem cell fate decision. Front. Cell Dev. Biol. 2020;8:611. doi 10.3389/FCELL.2020.00611Kulkarni R., Kale V. Physiological cues involved in the regulation of adhesion mechanisms in hematopoietic stem cell fate decision. Front. Cell Dev. Biol. 2020;8:611. doi 10.3389/FCELL.2020.00611Kumar S., Geiger H. HSC niche biology and HSC expansion ex vivo. Trends Mol. Med. 2017;23(9):799. doi 10.1016/J.MOLMED.2017.07.003Kumar S., Geiger H. HSC niche biology and HSC expansion ex vivo. Trends Mol. Med. 2017;23(9):799. doi 10.1016/J.MOLMED.2017.07.003Langston L.D., Symington L.S. Gene targeting in yeast is initiated by two independent strand invasions. Proc. Natl. Acad. Sci. USA. 2004; 101(43):15392-15397. doi 10.1073/PNAS.0403748101Langston L.D., Symington L.S. Gene targeting in yeast is initiated by two independent strand invasions. Proc. Natl. Acad. Sci. USA. 2004; 101(43):15392-15397. doi 10.1073/PNAS.0403748101Lauková L., Bertolo E.M.J., Zelinková M., Borbélyová V., Čonka J., Gaál Kovalčíková A., Domonkos E., Vlková B., Celec P. Early dynamics of plasma DNA in a mouse model of sepsis. Shock. 2019; 52(2):257-263. doi 10.1097/SHK.0000000000001215Lauková L., Bertolo E.M.J., Zelinková M., Borbélyová V., Čonka J., Gaál Kovalčíková A., Domonkos E., Vlková B., Celec P. Early dynamics of plasma DNA in a mouse model of sepsis. Shock. 2019; 52(2):257-263. doi 10.1097/SHK.0000000000001215Lévesque J.P., Helwani F.M., Winkler I.G. The endosteal ‘osteoblastic’ niche and its role in hematopoietic stem cell homing and mobilization. Leukemia. 2010;24(12):1979-1992. doi 10.1038/leu.2010.214Lévesque J.P., Helwani F.M., Winkler I.G. The endosteal ‘osteoblastic’ niche and its role in hematopoietic stem cell homing and mobilization. Leukemia. 2010;24(12):1979-1992. doi 10.1038/leu.2010.214Li J., Read L.R., Baker M.D. The mechanism of mammalian gene replacement is consistent with the formation of long regions of heteroduplex DNA associated with two crossing-over events. Mol. Cell. Biol. 2001;21(2):501-510. doi 10.1128/MCB.21.2.501-510.2001Li J., Read L.R., Baker M.D. The mechanism of mammalian gene replacement is consistent with the formation of long regions of heteroduplex DNA associated with two crossing-over events. Mol. Cell. Biol. 2001;21(2):501-510. doi 10.1128/MCB.21.2.501-510.2001Likhacheva A.S., Nikolin V.P., Popova N.A., Rogachev V.A., Prokhorovich M.A., Sebeleva T.E., Bogachev S.S., Shurdov M.A. Exogenous DNA can be captured by stem cells and be involved in their rescue from death after lethal-dose γ-radiation. Gene Therapy Mol. Biol. 2007;11:305-314Likhacheva A.S., Nikolin V.P., Popova N.A., Rogachev V.A., Prokhorovich M.A., Sebeleva T.E., Bogachev S.S., Shurdov M.A. Exogenous DNA can be captured by stem cells and be involved in their rescue from death after lethal-dose γ-radiation. Gene Therapy Mol. Biol. 2007;11:305-314Likhacheva A.S., Rogachev V.A., Nikolin V.P., Popova N.A., Shilov A.G., Sebeleva T.E., Strunkin D.N., Chernykh E.R., Gel’fgat E.L., Bogachev S.S., Shurdov M.A. Involvement of exogenous DNA in the molecular processes in somatic cell. Informatsionnyy Vestnik VOGiS = The Herald of Vavilov Society for Geneticists and Breeders. 2008;12(3):426-473 (in Russian)Likhacheva A.S., Rogachev V.A., Nikolin V.P., Popova N.A., Shilov A.G., Sebeleva T.E., Strunkin D.N., Chernykh E.R., Gel’fgat E.L., Bogachev S.S., Shurdov M.A. Involvement of exogenous DNA in the molecular processes in somatic cell. Informatsionnyy Vestnik VOGiS = The Herald of Vavilov Society for Geneticists and Breeders. 2008;12(3):426-473 (in Russian)Lucas D. Leukocyte trafficking and regulation of murine hematopoietic stem cells and their niches. Front. Immunol. 2019;10:387. doi 10.3389/FIMMU.2019.00387/BIBTEXLucas D. Leukocyte trafficking and regulation of murine hematopoietic stem cells and their niches. Front. Immunol. 2019;10:387. doi 10.3389/FIMMU.2019.00387/BIBTEXMaizels N., Davis L. Initiation of homologous recombination at DNA nicks. Nucleic Acids Res. 2018;46:6962-6973. doi 10.1093/NAR/GKY588Maizels N., Davis L. Initiation of homologous recombination at DNA nicks. Nucleic Acids Res. 2018;46:6962-6973. doi 10.1093/NAR/GKY588Maniatis T., Fritch E., Sambrook D. Methods of Genetic Engineering. Molecular Cloning. Moscow: Mir Publ., 1984 (in Russian)Maniatis T., Fritch E., Sambrook D. Methods of Genetic Engineering. Molecular Cloning. Moscow: Mir Publ., 1984 (in Russian)McMahon G., Alsina J.L., Levy S.B. Induction of a Ca2+, Mg2+-dependent endonuclease activity during the early stages of murine erythroleukemic cell differentiation. Proc. Natl. Acad. Sci. USA. 1984; 81(23):7461-7465. doi 10.1073/PNAS.81.23.7461McMahon G., Alsina J.L., Levy S.B. Induction of a Ca2+, Mg2+-dependent endonuclease activity during the early stages of murine erythroleukemic cell differentiation. Proc. Natl. Acad. Sci. USA. 1984; 81(23):7461-7465. doi 10.1073/PNAS.81.23.7461Mendelson A., Frenette P.S. Hematopoietic stem cell niche maintenance during homeostasis and regeneration. Nat. Med. 2014;20(8): 833-846. doi 10.1038/NM.3647Mendelson A., Frenette P.S. Hematopoietic stem cell niche maintenance during homeostasis and regeneration. Nat. Med. 2014;20(8): 833-846. doi 10.1038/NM.3647Morita Y., Ema H., Nakauchi H. Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment. J. Exp. Med. 2010;207(6):1173-1182. doi 10.1084/JEM.20091318Morita Y., Ema H., Nakauchi H. Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment. J. Exp. Med. 2010;207(6):1173-1182. doi 10.1084/JEM.20091318Muller-Sieburg C., Sieburg H.B. Stem cell aging: survival of the laziest? Cell Cycle. 2008;7(24):3798-3804. doi 10.4161/CC.7.24.7214Muller-Sieburg C., Sieburg H.B. Stem cell aging: survival of the laziest? Cell Cycle. 2008;7(24):3798-3804. doi 10.4161/CC.7.24.7214Patkin E.L., Kustova M.E., Noniashvili E.M. DNA-strand breaks in chromosomes of early mouse embryos as detected by in situ nick translation and gap filling. Genome. 1995;38:381-384. doi 10.1139/G95-049Patkin E.L., Kustova M.E., Noniashvili E.M. DNA-strand breaks in chromosomes of early mouse embryos as detected by in situ nick translation and gap filling. Genome. 1995;38:381-384. doi 10.1139/G95-049Petrova D.D., Dolgova E.V., Proskurina A.S., Ritter G.S., Ruzanova V.S., Efremov Y.R., Potter E.A., Kirikovich S.S., Levites E.V., Taranov O.S., Ostanin A.A., Chernykh E.R., Kolchanov N.A., Bogachev S.S. The new general biological property of stem-like tumor cells (Part II: Surface molecules, which belongs to distinctive groups with particular functions, form a unique pattern characteristic of a certain type of tumor stem-like cells). Int. J. Mol. Sci. 2022; 23(24):15800. doi 10.3390/ijms232415800Petrova D.D., Dolgova E.V., Proskurina A.S., Ritter G.S., Ruzanova V.S., Efremov Y.R., Potter E.A., Kirikovich S.S., Levites E.V., Taranov O.S., Ostanin A.A., Chernykh E.R., Kolchanov N.A., Bogachev S.S. The new general biological property of stem-like tumor cells (Part II: Surface molecules, which belongs to distinctive groups with particular functions, form a unique pattern characteristic of a certain type of tumor stem-like cells). Int. J. Mol. Sci. 2022; 23(24):15800. doi 10.3390/ijms232415800Pierce H., Zhang D., Magnon C., Lucas D., Christin J.R., Huggins M., Schwartz G.J., Frenette P.S. Cholinergic signals from the CNS regulate G-CSF-mediated HSC mobilization from bone marrow via a glucocorticoid signaling relay. Cell Stem. Cell. 2017;20:648-658.e4. doi 10.1016/J.STEM.2017.01.002Pierce H., Zhang D., Magnon C., Lucas D., Christin J.R., Huggins M., Schwartz G.J., Frenette P.S. Cholinergic signals from the CNS regulate G-CSF-mediated HSC mobilization from bone marrow via a glucocorticoid signaling relay. Cell Stem. Cell. 2017;20:648-658.e4. doi 10.1016/J.STEM.2017.01.002Pinho S., Frenette P.S. Haematopoietic stem cell activity and interactions with the niche. Nat. Rev. Mol. Cell Biol. 2019;20(5):303-320. doi 10.1038/S41580-019-0103-9Pinho S., Frenette P.S. Haematopoietic stem cell activity and interactions with the niche. Nat. Rev. Mol. Cell Biol. 2019;20(5):303-320. doi 10.1038/S41580-019-0103-9Potter E.A., Proskurina A.S., Ritter G.S., Dolgova E.V., Nikolin V.P., Popova N.A., Taranov O.S., Efremov Y.R., Bayborodin S.I., Ostanin A.A., Chernykh E.R., Kolchanov N.A., Bogachev S.S. Efficacy of a new cancer treatment strategy based on eradication of tumor-initiating stem cells in a mouse model of Krebs-2 solid adenocarcinoma. Oncotarget. 2018;9(47):28486-28499. doi 10.18632/oncotarget.25503Potter E.A., Proskurina A.S., Ritter G.S., Dolgova E.V., Nikolin V.P., Popova N.A., Taranov O.S., Efremov Y.R., Bayborodin S.I., Ostanin A.A., Chernykh E.R., Kolchanov N.A., Bogachev S.S. Efficacy of a new cancer treatment strategy based on eradication of tumor-initiating stem cells in a mouse model of Krebs-2 solid adenocarcinoma. Oncotarget. 2018;9(47):28486-28499. doi 10.18632/oncotarget.25503Potter E.A., Dolgova E.V., Proskurina A.S., Ruzanova V.S., Efremov Y.R., Kirikovich S.S., Oshikhmina S.G., Mamaev A.L., Taranov O.S., Bryukhovetskiy A.S., Grivtsova L.U., Kolchanov N.A., Os-tanin A.A., Chernykh E.R., Bogachev S.S. Stimulation of mouse hematopoietic stem cells by angiogenin and DNA preparations. Braz. J. Med. Biol. Res. 2024;57:e13072. doi 10.1590/1414-431X2024E13072Potter E.A., Dolgova E.V., Proskurina A.S., Ruzanova V.S., Efremov Y.R., Kirikovich S.S., Oshikhmina S.G., Mamaev A.L., Taranov O.S., Bryukhovetskiy A.S., Grivtsova L.U., Kolchanov N.A., Os-tanin A.A., Chernykh E.R., Bogachev S.S. Stimulation of mouse hematopoietic stem cells by angiogenin and DNA preparations. Braz. J. Med. Biol. Res. 2024;57:e13072. doi 10.1590/1414-431X2024E13072Pulito V.L., Miller D.L., Sassa S., Yamane T. DNA fragments in Friend erythroleukemia cells induced by dimethyl sulfoxide. Proc. Natl. Acad. Sci. USA. 1983;80(19):5912-5915. doi 10.1073/PNAS.80.19.5912Pulito V.L., Miller D.L., Sassa S., Yamane T. DNA fragments in Friend erythroleukemia cells induced by dimethyl sulfoxide. Proc. Natl. Acad. Sci. USA. 1983;80(19):5912-5915. doi 10.1073/PNAS.80.19.5912Rass E., Grabarz A., Bertrand P., Lopez B.S. Double strand break repair, one mechanism can hide another: alternative non-homologous end joining. Cancer Radiother. 2012;16:1-10. doi 10.1016/J.CANRAD.2011.05.004Rass E., Grabarz A., Bertrand P., Lopez B.S. Double strand break repair, one mechanism can hide another: alternative non-homologous end joining. Cancer Radiother. 2012;16:1-10. doi 10.1016/J.CANRAD.2011.05.004Redondo P.A., Pavlou M., Loizidou M., Cheema U. Elements of the niche for adult stem cell expansion. J. Tissue Eng. 2017;8: 2041731417725464. doi 10.1177/2041731417725464Redondo P.A., Pavlou M., Loizidou M., Cheema U. Elements of the niche for adult stem cell expansion. J. Tissue Eng. 2017;8: 2041731417725464. doi 10.1177/2041731417725464Ritter G.S., Dolgova E.V., Petrova D.D., Efremov Y.R., Proskurina A.S., Potter E.A., Ruzanova V.S., Kirikovich S.S., Levites E.V., Taranov O.S., Ostanin A.A., Chernykh E.R., Kolchanov N.A., Bogachev S.S. The new general biological property of stem-like tumor cells. Part I. Peculiarities of the process of the double-stranded DNA fragments internalization into stem-like tumor cells. Front. Genetics. 2022;13:954395. doi 10.3389/fgene.2022.954395Ritter G.S., Dolgova E.V., Petrova D.D., Efremov Y.R., Proskurina A.S., Potter E.A., Ruzanova V.S., Kirikovich S.S., Levites E.V., Taranov O.S., Ostanin A.A., Chernykh E.R., Kolchanov N.A., Bogachev S.S. The new general biological property of stem-like tumor cells. Part I. Peculiarities of the process of the double-stranded DNA fragments internalization into stem-like tumor cells. Front. Genetics. 2022;13:954395. doi 10.3389/fgene.2022.954395Rix B., Maduro A.H., Bridge K.S., Grey W. Markers for human haematopoietic stem cells: the disconnect between an identification marker and its function. Front. Physiol. 2022;13. doi 10.3389/FPHYS.2022.1009160Rix B., Maduro A.H., Bridge K.S., Grey W. Markers for human haematopoietic stem cells: the disconnect between an identification marker and its function. Front. Physiol. 2022;13. doi 10.3389/FPHYS.2022.1009160Rubnitz J., Subramani S. The minimum amount of homology required for homologous recombination in mammalian cells. Mol. Cell. Biol. 1984;4(11):2253-2258. doi 10.1128/MCB.4.11.2253-2258.1984Rubnitz J., Subramani S. The minimum amount of homology required for homologous recombination in mammalian cells. Mol. Cell. Biol. 1984;4(11):2253-2258. doi 10.1128/MCB.4.11.2253-2258.1984Ruzanova V., Proskurina A., Efremov Y., Kirikovich S., Ritter G., Levites E., Dolgova E., Potter E., Babaeva O., Sidorov S., Taranov O., Ostanin A., Chernykh E., Bogachev S. Chronometric administration of cyclophosphamide and a double-stranded DNA-Mix at interstrand crosslinks repair timing, called “Karanahan” therapy, is highly efficient in a weakly immunogenic Lewis carcinoma model. Pathol. Oncol. Res. 2022;28. doi 10.3389/PORE.2022.1610180Ruzanova V., Proskurina A., Efremov Y., Kirikovich S., Ritter G., Levites E., Dolgova E., Potter E., Babaeva O., Sidorov S., Taranov O., Ostanin A., Chernykh E., Bogachev S. Chronometric administration of cyclophosphamide and a double-stranded DNA-Mix at interstrand crosslinks repair timing, called “Karanahan” therapy, is highly efficient in a weakly immunogenic Lewis carcinoma model. Pathol. Oncol. Res. 2022;28. doi 10.3389/PORE.2022.1610180Saitoh T., Fujita N., Yoshimori T., Akira S. Regulation of dsDNAinduced innate immune responses by membrane trafficking. Autophagy. 2010;6:430-432. doi 10.4161/AUTO.6.3.11611Saitoh T., Fujita N., Yoshimori T., Akira S. Regulation of dsDNAinduced innate immune responses by membrane trafficking. Autophagy. 2010;6:430-432. doi 10.4161/AUTO.6.3.11611Scharf P., Broering M.F., da Rocha G.H.O., Farsky S.H.P. Cellular and molecular mechanisms of environmental pollutants on hematopoiesis. Int. J. Mol. Sci. 2020;21(19):6996. doi 10.3390/IJMS21196996Scharf P., Broering M.F., da Rocha G.H.O., Farsky S.H.P. Cellular and molecular mechanisms of environmental pollutants on hematopoiesis. Int. J. Mol. Sci. 2020;21(19):6996. doi 10.3390/IJMS21196996Scher W., Friend C. Breakage of DNA and alterations in folded genomes by inducers of differentiation in Friend erythroleukemic cells. Cancer Res. 1978;38:841-849Scher W., Friend C. Breakage of DNA and alterations in folded genomes by inducers of differentiation in Friend erythroleukemic cells. Cancer Res. 1978;38:841-849Seita J., Weissman I.L. Hematopoietic stem cell: self-renewal versus differentiation. Wiley Interdiscip. Rev. Syst. Biol. Med. 2010;2(6): 640-653. doi 10.1002/WSBM.86Seita J., Weissman I.L. Hematopoietic stem cell: self-renewal versus differentiation. Wiley Interdiscip. Rev. Syst. Biol. Med. 2010;2(6): 640-653. doi 10.1002/WSBM.86Silberstein L., Goncalves K.A., Kharchenko P.V., Turcotte R., Kfoury Y., Mercier F., Baryawno N., Severe N., Bachand J., Spencer J.A., Papazian A., Lee D., Chitteti B.R., Srour E.F., Hoggatt J., Tate T., Lo Celso C., Ono N., Nutt S., Heino J., Sipilä K., Shioda T., Osawa M., Lin C.P., Hu G.-fu, Scadden D.T. Proximity-based differential single-cell analysis of the niche to identify stem/progenitor cell regulators. Cell Stem Cell. 2016;19(4):530-543. doi 10.1016/J.STEM.2016.07.004Silberstein L., Goncalves K.A., Kharchenko P.V., Turcotte R., Kfoury Y., Mercier F., Baryawno N., Severe N., Bachand J., Spencer J.A., Papazian A., Lee D., Chitteti B.R., Srour E.F., Hoggatt J., Tate T., Lo Celso C., Ono N., Nutt S., Heino J., Sipilä K., Shioda T., Osawa M., Lin C.P., Hu G.-fu, Scadden D.T. Proximity-based differential single-cell analysis of the niche to identify stem/progenitor cell regulators. Cell Stem Cell. 2016;19(4):530-543. doi 10.1016/J.STEM.2016.07.004So A., Le Guen T., Lopez B.S., Guirouilh-Barbat J. Genomic rearrangements induced by unscheduled DNA double strand breaks in somatic mammalian cells. FEBS J. 2017;284(15):2324-2344. doi 10.1111/FEBS.14053So A., Le Guen T., Lopez B.S., Guirouilh-Barbat J. Genomic rearrangements induced by unscheduled DNA double strand breaks in somatic mammalian cells. FEBS J. 2017;284(15):2324-2344. doi 10.1111/FEBS.14053Szade K., Gulati G.S., Chan C.K.F., Kao K.S., Miyanishi M., Marjon K.D., Sinha R., George B.M., Chen J.Y., Weissman I.L. Where hematopoietic stem cells live: the bone marrow niche. Antioxid. Redox Signal. 2018;29:191. doi 10.1089/ARS.2017.7419Szade K., Gulati G.S., Chan C.K.F., Kao K.S., Miyanishi M., Marjon K.D., Sinha R., George B.M., Chen J.Y., Weissman I.L. Where hematopoietic stem cells live: the bone marrow niche. Antioxid. Redox Signal. 2018;29:191. doi 10.1089/ARS.2017.7419Vatolin S.Y., Okhapkina E.V., Matveeva N.M., Shilov A.G., Baiborodin S.I., Philimonenko V.V., Zhdanova N.S., Serov O.L. Scheduled perturbation in DNA during in vitro differentiation of mouse embryo-derived cells. Mol. Reprod. Dev. 1997;47(1):1-10. doi 10.1002/(SICI)1098-2795(199705)47:1<1::AID-MRD1>3.0.CO;2-RVatolin S.Y., Okhapkina E.V., Matveeva N.M., Shilov A.G., Baiborodin S.I., Philimonenko V.V., Zhdanova N.S., Serov O.L. Scheduled perturbation in DNA during in vitro differentiation of mouse embryo-derived cells. Mol. Reprod. Dev. 1997;47(1):1-10. doi 10.1002/(SICI)1098-2795(199705)47:1<1::AID-MRD1>3.0.CO;2-RVriend L.E.M., Krawczyk P.M. Nick-initiated homologous recombination: protecting the genome, one strand at a time. DNA Repair. 2017; 50:1-13. doi 10.1016/J.DNAREP.2016.12.005Vriend L.E.M., Krawczyk P.M. Nick-initiated homologous recombination: protecting the genome, one strand at a time. DNA Repair. 2017; 50:1-13. doi 10.1016/J.DNAREP.2016.12.005Wang S., Zhang Y., Meng W., Dong Y., Zhang S., Teng L., Liu Y., Li L., Wang D. The involvement of macrophage colony stimulating factor on protein hydrolysate injection mediated hematopoietic function improvement. Cells. 2021;10(10):2776. doi 10.3390/CELLS10102776Wang S., Zhang Y., Meng W., Dong Y., Zhang S., Teng L., Liu Y., Li L., Wang D. The involvement of macrophage colony stimulating factor on protein hydrolysate injection mediated hematopoietic function improvement. Cells. 2021;10(10):2776. doi 10.3390/CELLS10102776Wilkinson A.C., Igarashi K.J., Nakauchi H. Haematopoietic stem cell self-renewal in vivo and ex vivo. Nat. Rev. Genet. 2020;21(9):541-554. doi 10.1038/s41576-020-0241-0Wilkinson A.C., Igarashi K.J., Nakauchi H. Haematopoietic stem cell self-renewal in vivo and ex vivo. Nat. Rev. Genet. 2020;21(9):541-554. doi 10.1038/s41576-020-0241-0Winkler I.G., Barbier V., Nowlan B., Jacobsen R.N., Forristal C.E., Patton J.T., Magnani J.L., Lévesque J.P. Vascular niche E-selectin regulates hematopoietic stem cell dormancy, self renewal and chemoresistance. Nat. Med. 2012;18(11):1651-1657. doi 10.1038/NM.2969Winkler I.G., Barbier V., Nowlan B., Jacobsen R.N., Forristal C.E., Patton J.T., Magnani J.L., Lévesque J.P. Vascular niche E-selectin regulates hematopoietic stem cell dormancy, self renewal and chemoresistance. Nat. Med. 2012;18(11):1651-1657. doi 10.1038/NM.2969Xu S.Y. Sequence-specific DNA nicking endonucleases. Biomol. Concepts. 2015;6(4):253-267. doi 10.1515/BMC-2015-0016Xu S.Y. Sequence-specific DNA nicking endonucleases. Biomol. Concepts. 2015;6(4):253-267. doi 10.1515/BMC-2015-0016Zhang C.C., Sadek H.A. Hypoxia and metabolic properties of hematopoietic stem cells. Antioxid. Redox. Signal. 2014;20(12):1891-1901. doi 10.1089/ARS.2012.5019Zhang C.C., Sadek H.A. Hypoxia and metabolic properties of hematopoietic stem cells. Antioxid. Redox. Signal. 2014;20(12):1891-1901. doi 10.1089/ARS.2012.5019Zilio N., Ulrich H.D. Exploring the SSBreakome: genome-wide mapping of DNA single-strand breaks by next-generation sequencing. FEBS J. 2021;288(13):3948-3961. doi 10.1111/FEBS.15568Zilio N., Ulrich H.D. Exploring the SSBreakome: genome-wide mapping of DNA single-strand breaks by next-generation sequencing. FEBS J. 2021;288(13):3948-3961. doi 10.1111/FEBS.15568

The authors declare that there are no conflicts of interest present.