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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">vavilov</journal-id><journal-title-group><journal-title xml:lang="ru">Вавиловский журнал генетики и селекции</journal-title><trans-title-group xml:lang="en"><trans-title>Vavilov Journal of Genetics and Breeding</trans-title></trans-title-group></journal-title-group><issn pub-type="epub">2500-3259</issn><publisher><publisher-name>Institute of Cytology and Genetics of Siberian Branch of the RAS</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.18699/vjgb-26-40</article-id><article-id custom-type="elpub" pub-id-type="custom">vavilov-5103</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>МОЛЕКУЛЯРНАЯ И КЛЕТОЧНАЯ БИОЛОГИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>MOLECULAR AND CELL BIOLOGY</subject></subj-group></article-categories><title-group><article-title>Получение линий индуцированных плюрипотентных стволовых клеток RCPCMi014-A и RCPCMi014-B из Т-лимфоцитов здорового донора и верификация их моноклонального происхождения по V(D)J-перестройкам генов TCR</article-title><trans-title-group xml:lang="en"><trans-title>Generation of the RCPCMi014-A and RCPCMi014-B lines from T-lymphocytes of a healthy donor and verification of their monoclonal origin by TCR V(D)J rearrangement analysis</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Шерман</surname><given-names>Д. К.</given-names></name><name name-style="western" xml:lang="en"><surname>Sherman</surname><given-names>D. K.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва</p></bio><bio xml:lang="en"><p>Moscow</p></bio><email xlink:type="simple">dar.sher.man0@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Богомякова</surname><given-names>М. Е.</given-names></name><name name-style="western" xml:lang="en"><surname>Bogomiakova</surname><given-names>M. E.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва</p></bio><bio xml:lang="en"><p>Moscow</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кастуева</surname><given-names>Э. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Kastueva</surname><given-names>E. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва</p></bio><bio xml:lang="en"><p>Moscow</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Звягин</surname><given-names>И. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Zvyagin</surname><given-names>I. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва</p></bio><bio xml:lang="en"><p>Moscow</p></bio><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Руппель</surname><given-names>В. К.</given-names></name><name name-style="western" xml:lang="en"><surname>Ruppel</surname><given-names>V. K.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва</p></bio><bio xml:lang="en"><p>Moscow</p></bio><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Барсова</surname><given-names>Е. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Barsova</surname><given-names>E. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва</p></bio><bio xml:lang="en"><p>Moscow</p></bio><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Горбачев</surname><given-names>А. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Gorbachev</surname><given-names>A. Y.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва</p></bio><bio xml:lang="en"><p>Moscow</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кулемин</surname><given-names>Н. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Kulemin</surname><given-names>N. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва</p></bio><bio xml:lang="en"><p>Moscow</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Баринова</surname><given-names>А. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Barinova</surname><given-names>A. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва</p></bio><bio xml:lang="en"><p>Moscow</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Зеркаленкова</surname><given-names>Е. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Zerkalenkova</surname><given-names>E. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва</p></bio><bio xml:lang="en"><p>Moscow</p></bio><xref ref-type="aff" rid="aff-5"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Богомазова</surname><given-names>А. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Bogomazova</surname><given-names>A. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва</p></bio><bio xml:lang="en"><p>Moscow</p></bio><xref ref-type="aff" rid="aff-6"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Лагарькова</surname><given-names>М. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Lagarkova</surname><given-names>M. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Москва</p></bio><bio xml:lang="en"><p>Moscow</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru">Федеральный научно-клинический центр физико-химической медицины им. академика Ю.М. Лопухина Федерального медико-биологического агентства России<country>Россия</country></aff><aff xml:lang="en">Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru">Федеральный научно-клинический центр физико-химической медицины им. академика Ю.М. Лопухина Федерального медико-биологического агентства России;&#13;
Центр «Генетическое репрограммирование и генная терапия» Федерального научно клинического центра физико-химической медицины им. академика Ю.М. Лопухина Федерального медико-биологического агентства России<country>Россия</country></aff><aff xml:lang="en">Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency;&#13;
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru">Государственный научный центр Российской Федерации Институт биоорганической химии им. академиков М.М. Шемякина и Ю.А. Овчинникова Российской академии наук<country>Россия</country></aff><aff xml:lang="en">Shemyakin−Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-4"><aff xml:lang="ru">Государственный научный центр Российской Федерации Институт биоорганической химии им. академиков М.М. Шемякина и Ю.А. Овчинникова Российской академии наук;&#13;
ООО «Майлаборатори»<country>Россия</country></aff><aff xml:lang="en">Shemyakin−Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences;&#13;
LLC “MiLaboratori”<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-5"><aff xml:lang="ru">Национальный медицинский исследовательский центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева Министерства здравоохранения Российской Федерации;&#13;
Российский национальный исследовательский медицинский университет им. Н.И. Пирогова Министерства здравоохранения Российской Федерации<country>Россия</country></aff><aff xml:lang="en">Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology;&#13;
Pirogov Russian National Research Medical University<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-6"><aff xml:lang="ru">Федеральный научно-клинический центр физико-химической медицины им. академика Ю.М. Лопухина Федерального медико-биологического агентства России;&#13;
Центр «Генетическое репрограммирование и генная терапия» Федерального научно-клинического центра физико-химической медицины им. академика Ю.М. Лопухина Федерального медико-биологического агентства России<country>Россия</country></aff><aff xml:lang="en">Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency;&#13;
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency<country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2026</year></pub-date><pub-date pub-type="epub"><day>26</day><month>05</month><year>2026</year></pub-date><volume>30</volume><issue>3</issue><fpage>362</fpage><lpage>371</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Шерман Д.К., Богомякова М.Е., Кастуева Э.А., Звягин И.В., Руппель В.К., Барсова Е.В., Горбачев А.Ю., Кулемин Н.А., Баринова А.А., Зеркаленкова Е.А., Богомазова А.Н., Лагарькова М.А., 2026</copyright-statement><copyright-year>2026</copyright-year><copyright-holder xml:lang="ru">Шерман Д.К., Богомякова М.Е., Кастуева Э.А., Звягин И.В., Руппель В.К., Барсова Е.В., Горбачев А.Ю., Кулемин Н.А., Баринова А.А., Зеркаленкова Е.А., Богомазова А.Н., Лагарькова М.А.</copyright-holder><copyright-holder xml:lang="en">Sherman D.K., Bogomiakova M.E., Kastueva E.A., Zvyagin I.V., Ruppel V.K., Barsova E.V., Gorbachev A.Y., Kulemin N.A., Barinova A.A., Zerkalenkova E.A., Bogomazova A.N., Lagarkova M.A.</copyright-holder><license license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://vavilov.elpub.ru/jour/article/view/5103">https://vavilov.elpub.ru/jour/article/view/5103</self-uri><abstract><p>Получение индуцированных плюрипотентных стволовых клеток из Т-лимфоцитов периферической крови представляет собой перспективную альтернативу использованию фибробластов кожи. Этот подход сочетает минимально инвазивный забор биоматериала совместно с быстрым получением обогащенной популяции целевых клеток. Дополнительным преимуществом является относительно низкий мутационный груз T-лимфоцитов по сравнению с традиционным источником соматических клеток для репрограммирования – фибробластами кожи, ввиду того что Т-лимфоциты защищены от хронического воздействия ультрафиолетового излучения – одного из ключевых факторов накопления соматических мутаций. Объективная верификация моноклональности полученных линий индуцированных плюрипотентных стволовых клеток возможна благодаря наличию V(D)J-перестроек генов Т-клеточного рецептора, формирующихся в результате соматической рекомбинации в тимусе в процессе естественного созревания Т-лимфоцитов. Эти перестройки остаются неизменными при репрограммировании и служат уникальным маркером, позволяющим достоверно идентифицировать моноклональные линии и исключать контаминированные линии или линии поликлонального происхождения. Надежная верификация клонального происхождения индуцированных плюрипотентных стволовых клеток может быть важной в экспериментах, предъявляющих высокие требования к генетической однородности. Данная работа посвящена созданию и комплексной характеристике моноклональных линий индуцированных плюрипотентных стволовых клеток, полученных из CD3+ Т-лимфоцитов здорового донора методом эписомного репрограммирования. Полученные линии RCPCMi014-A (PBM022E5) и RCPCMi014-B (PBM022E7) соответствуют принятым критериям качества для индуцированных плюрипотентных стволовых клеток: они демонстрируют экспрессию ключевых маркеров плюрипотентности (OCT4, SOX2, SSEA-4, TRA-1-81), способность к дифференцировке в производные всех трех зародышевых листков и обладают нормальным кариотипом. Обе линии показали способность к дифференцировке в дефинитивную эндодерму с высокой эффективностью, оцененной по экспрессии CXCR4, что определяет их перспективность для разработки протоколов генерации β-клеток поджелудочной железы. Полученные линии индуцированных плюрипотентных стволовых клеток могут быть использованы для фундаментальных исследований механизмов плюрипотентности и дифференцировки, а также для создания изогенных линий индуцированных плюрипотентных стволовых клеток с внесенными мутациями при моделировании редких наследственных заболеваний.</p></abstract><trans-abstract xml:lang="en"><p>The generation of induced pluripotent stem cells (iPSCs) from peripheral blood T-lymphocytes offers a promising alternative to skin fibroblasts. This approach combines minimally invasive sample collection with rapid isolation of enriched target cell population and provides a lower baseline mutational burden, as T-lymphocytes are shielded from chronic ultraviolet radiation – a major driver of somatic mutations in skin fibroblasts. Objective verification of monoclonality of the resulting iPSC lines is possible due to V(D)J rearrangements in T-cell receptor (TCR) genes, which are formed as a result of somatic recombination in the thymus during the natural maturation of T-lymphocytes. These rearrangements remain unchanged during reprogramming and serve as a unique marker, allowing for reliable identification of monoclonal lines and exclusion of contaminated or polyclonal lines. Reliable verification of the clonal origin of iPSCs can be crucial in experiments that place high demands on genetic homogeneity. This work is dedicated to the generation and comprehensive characterization of monoclonal iPSC lines derived from CD3+ T-lymphocytes of a healthy donor using episomal reprogramming. The resulting lines, RCPCMi014-A (PBM022E5) and RCPCMi014-B (PBM022E7), meet the accepted quality criteria for iPSCs: they demonstrate expression of key pluripotency markers (OCT4, SOX2, SSEA-4, TRA-1-81), the ability to differentiate into derivatives of all three germ layers, and possess a normal karyotype. Both lines showed a high-efficiency capacity to differentiate into definitive endoderm, as assessed by CXCR4 expression, highlighting their potential for developing protocols to generate pancreatic β-cells. The obtained iPSC lines can be used for fundamental research into the mechanisms of pluripotency and differentiation, as well as for creating isogenic iPSC lines with introduced mutations for modeling rare hereditary diseases.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>индуцированные плюрипотентные стволовые клетки</kwd><kwd>Т-лимфоциты</kwd><kwd>репрограммирование</kwd><kwd>T-клеточный рецептор</kwd><kwd>клон клеток</kwd><kwd>V(D)J-рекомбинация</kwd><kwd>дефинитивная эндодерма</kwd></kwd-group><kwd-group xml:lang="en"><kwd>induced pluripotent stem cells</kwd><kwd>T-lymphocytes</kwd><kwd>reprogramming</kwd><kwd>T-cell receptor</kwd><kwd>cell clone</kwd><kwd>V(D)J recombination</kwd><kwd>definitive endoderm</kwd></kwd-group><funding-group xml:lang="en"><funding-statement>The study was carried out with the financial support of the Ministry of Science and Higher Education of the Russian Federation (The Federal Scientific and Technical Program for the Development of Genetic Technologies 2019– 2030, project No. 075-15-2025-518)</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Alt F.W., Oltz E.M., Young F., Gorman J., Taccioli G., Chen J. 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