vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/vjgb-25-52vavilov-4674Research ArticleМОЛЕКУЛЯРНАЯ И КЛЕТОЧНАЯ БИОЛОГИЯMOLECULAR AND CELL BIOLOGYКонцепция природной реконструкции генома. Часть 3. Анализ изменения количества теломерной ДНК в клетках колоний как нового амплифицированного признака, возникшего при обработке гемопоэтических стволовых клеток костного мозгаConcept of natural genome reconstruction. Part 3. Analysis of changes in the amount of telomeric DNA in colony cells as a new amplified feature that arose during the processing of hematopoietic bone marrow stem cellsРузановаВ. С.RuzanovaV. S.

Новоси6ирск

Novosibirsk

ОшихминаС. Г.OshikhminaS. G.

Новоси6ирск

Novosibirsk

РиттерГ. С.RitterG. S.

Новоси6ирск

Novosibirsk

ДолговаЕ. В.DolgovaE. V.

Новоси6ирск

Novosibirsk

КириковичС. С.KirikovichS. S.

Новоси6ирск

Novosibirsk

ЛевитесЕ. В.LevitesE. V.

Новоси6ирск

Novosibirsk

ЕфремовЯ. Р.EfremovY. R.

Новоси6ирск

Novosibirsk

КарамышеваТ. В.KaramyshevaT. V.

Новоси6ирск

Novosibirsk

БогомоловА. Г.BogomolovA. G.

Новоси6ирск

Novosibirsk

МещаниноваМ. И.MeschaninovaM. I.

Новоси6ирск

Novosibirsk

МамаевА. Л.MamaevA. L.

Новоси6ирск

Novosibirsk

ТарановО. С.TaranovO. S.

р. п. Кольцово, Новоси6ирская о6ласть

Koltsovo, Novosibirsk region

СидоровС. В.SidorovS. V.

Новоси6ирск

Novosibirsk

НиконовС. Д.NikonovS. D.

Новоси6ирск

Novosibirsk

ЛеплинаО. Ю.LeplinaO. Y.

Новоси6ирск

Novosibirsk

ОстанинА. А.OstaninA. A.

Новоси6ирск

Novosibirsk

ЧерныхЕ. Р.ChernykhE. R.

Новоси6ирск

Novosibirsk

КолчановН. А.KolchanovN. A.

Новоси6ирск

Novosibirsk

ПроскуринаА. С.ProskurinaA. S.

Новоси6ирск

Novosibirsk

БогачевС. С.BogachevS. S.

Новоси6ирск

Novosibirsk

labmolbiol@mail.ruФедеральный исследовательский центр Институт цитологии и генетики Си6ирского отделения Российской академии наукРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesRussian FederationФедеральный исследовательский центр Институт цитологии и генетики Си6ирского отделения Российской академии наук; Новоси6ирский национальный исследовательский государственный университетРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State UniversityRussian FederationИнститут химической 6иологии и фундаментальной медицины Си6ирского отделения Российской академии наукРоссияInstitute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of SciencesRussian FederationOOO «Ла6оратория Ангиофарм»РоссияLaboratory Angiopharm LLCRussian FederationГосударственный научный центр вирусологии и 6иотехнологии «Bектор» Роспотре6надзораРоссияState Scientific Center of Virology and Biotechnology “Vector” of RospotrebnadzorRussian FederationНовоси6ирский национальный исследовательский государственный университет; Городская клиническая 6ольница № 1РоссияNovosibirsk State University; City Clinical Hospital No. 1Russian FederationНовоси6ирский научно-исследовательский институт ту6еркулезаРоссияNovosibirsk Tuberculosis Research InstituteRussian FederationНаучно-исследовательский институт фундаментальной и клинической иммунологииРоссияResearch Institute of Fundamental and Clinical ImmunologyRussian Federation202520072025294479495Copyright © Рузанова В.С., Ошихмина С.Г., Риттер Г.С., Долгова Е.В., Кирикович С.С., Левитес Е.В., Ефремов Я.Р., Карамышева Т.В., Богомолов А.Г., Мещанинова М.И., Мамаев А.Л., Таранов О.С., Сидоров С.В., Никонов С.Д., Леплина О.Ю., Останин А.А., Черных Е.Р., Колчанов Н.А., Проскурина А.С., Богачев С.С., 20252025Рузанова В.С., Ошихмина С.Г., Риттер Г.С., Долгова Е.В., Кирикович С.С., Левитес Е.В., Ефремов Я.Р., Карамышева Т.В., Богомолов А.Г., Мещанинова М.И., Мамаев А.Л., Таранов О.С., Сидоров С.В., Никонов С.Д., Леплина О.Ю., Останин А.А., Черных Е.Р., Колчанов Н.А., Проскурина А.С., Богачев С.С.Ruzanova V.S., Oshikhmina S.G., Ritter G.S., Dolgova E.V., Kirikovich S.S., Levites E.V., Efremov Y.R., Karamysheva T.V., Bogomolov A.G., Meschaninova M.I., Mamaev A.L., Taranov O.S., Sidorov S.V., Nikonov S.D., Leplina O.Y., Ostanin A.A., Chernykh E.R., Kolchanov N.A., Proskurina A.S., Bogachev S.S.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/4674

Индуцированная «реком6иногенная ситуация» в гемопоэтических стволовых клетках и активация репаративных систем клетки создают основу для реком6инационных со6ытий между доставленными в клетку фрагментами экстраклеточной двуцепочечной ДНК и ДНК хромосом или иных форм репаративно-реком6инационного процесса. На модельных организмах мыши и крысы, а также с использованием в качестве исходного материала клеток костного мозга человека 6ыло оценено изменение количества теломерной ДНК в гемопоэтических стволовых клетках как показатель произошедших репарационно-реком6инационных со6ытий. Bо всех проведенных экспериментах в качестве фактора сравнения использовался ангиогенин реком6инантный человеческий. Методом дот-6лот ги6ридизации показано, что в клетках колоний, полученных из клеток костного мозга модельных организмов, а также из клеток о6разцов костного мозга человека, о6ра6отанных препаратом двуцепочечной ДНК, произошло достоверное увеличение количества теломерной ДНК. Амплификация теломерной ДНК в клетках колоний не связана с контаминацией препаратом исходной ДНК, которым о6ра6атывались клетки костного мозга. O6ра6отка клеток костного мозга ДНК, не несущей теломерных последовательностей (AluI ПЦР-фрагмент), не приводит к увеличению количества теломерной ДНК в клетках выросших колоний. Это предполагает участие в амплификации теломерной ДНК экстрахромосомальной ДНК-матрицы, несущей ДНК теломер. Установлено, что о6ра6отка клеток костного мозга ангиогенином также сопровождается увеличением теломерной ДНК в клетках колоний. Сопоставление типа колоний с интенсивностью ги6ридизации (т. е. количества теломерной ДНК в о6разце) предполагало, что увеличение количества детектируемой теломерной ДНК при о6ра6отке ангиогенином и hDNAgr имеет принципиально разное происхождение. Bестерн-6лот анализом и методом ПЦР в реальном времени установлено, что увеличение количества теломерной ДНК при о6ра6отке клеток костного мозга препаратом двуцепочечной ДНК не коррелирует с активностью эндогенной/экзогенной теломеразы. Для ангиогенина показано, что увеличение количества теломерной ДНК может 6ыть результатом активации эндогенной теломеразной активности. Разра6отан принцип амплификации нового генетического признака, пришедшего в гемопоэтические стволовые клетки с экстраклеточным двуцепочечным ДНК материалом и закрепившимся в реципиентном геноме или транзитно присутствующим в клетке в качестве новой генетической информации.

The induced “recombinogenic situation” in hematopoietic stem cells and the activation of the cell’s reparative systems create the basis for recombination events between fragments of extracellular double-stranded DNA delivered into the cell and chromosomal DNA or other forms of the reparative-recombination process. In mouse and rat model organisms as well as in human bone marrow cells, changes in the amount of telomeric DNA in hematopoietic stem cells were assessed as an indicator of repair and recombination events that have occurred. In all experiments performed, recombinant human angiogenin was used as a comparison factor. Dot blot hybridization showed that in the colony cells obtained from the bone marrow cells of the model organisms as well as from human bone marrow cells treated with a double-stranded DNA preparation, there was a significant increase in the amount of telomeric DNA. Amplification of telomeric DNA in colony cells is not associated with contamination of the original DNA preparation with which the bone marrow cells were treated. Treatment of bone marrow cells with DNA that does not carry telomeric sequences (AluI PCR fragment) does not lead to an increase in the amount of telomeric DNA in the cells of grown colonies. This suggests the participation in the amplification of telomeric DNA of an extrachromosomal DNA template carrying telomeric DNA. It has been established that treatment of bone marrow cells with angiogenin also leads to an increase in telomeric DNA in colony cells. A comparison of the type of colonies with the intensity of hybridization (i. e. the amount of telomeric DNA in the sample) suggests that the increase in the amount of detectable telomeric DNA following treatment with angiogenin and hDNAgr has a fundamentally different origin. Western blot analysis and real-time PCR revealed that the increase in the amount of telomeric DNA following treatment of bone marrow cells with a double-stranded DNA preparation does not correlate with the activity of endogenous/exogenous telomerase. For angiogenin, it has been shown that an increase in the amount of telomeric DNA may be the result of activation of endogenous telomerase activity. A principle has been developed for the amplification of a new genetic trait that came into hematopoietic stem cells with extracellular double-stranded DNA material and was fixed in the recipient genome or was transitively present in the cell as new genetic information.

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