- Код статьи
- 10.31857/S0475145023020052-1
- DOI
- 10.31857/S0475145023020052
- Тип публикации
- Статус публикации
- Опубликовано
- Авторы
- Том/ Выпуск
- Том 54 / Номер выпуска 2
- Страницы
- 148-161
- Аннотация
- Современные исследования плюрипотентных стволовых клеток (ПСК) человека ставят своей задачей подбор условий и факторов роста, которые позволят лучше имитировать преимплантационное развитие и дифференцировку зародышевых клеток, что имеет важное значение для создания клеточных моделей заболеваний. Ранее было показано, что в присутствии хемокина CCL2 ПСК человека приобретают свойства, присущие преимплантационным бластомерам, а именно активируют сигнальный путь JAK-STAT3 и повышают уровень мРНК генов гипоксического ответа. Однако CCL2 практически не используется при культивировании ПСК человека, а его действие описано в единственном исследовании. Мы продолжили изучение влияния CCL2 на ПСК человека и показали, что эмбриональные и индуцированные плюрипотентные стволовые клетки человека, культивированные с CCL2, имеют повышенный уровень белка кислородзависимых субъединиц HIF1A и HIF2A, необходимых для запуска гипоксического ответа, а также повышенный уровень белков ключевых транскрипционных факторов плюрипотентности OCT4, NANOG, KLF4, SOX2 и TFCP2L1. Кроме того, присутствие CCL2 положительно влияет на направленную эндотелиальную дифференцировку, ускоряя созревание предшественников и усиливая ангиогенный потенциал дифференцированных производных.
- Ключевые слова
- плюрипотентные стволовые клетки хемокин CCL2 гипоксический ответ направленная эндотелиальная дифференцировка
- Дата публикации
- 18.09.2025
- Год выхода
- 2025
- Всего подписок
- 0
- Всего просмотров
- 13
Библиография
- 1. An C., Feng G., Zhang J. et al. Overcoming autocrine FGF signaling-induced heterogeneity in naive human ESCs enables modeling of random X chromosome inactivation // Cell Stem Cell. 2020. V. 27. № 3. P. 482–497.e4.
- 2. Baay-Guzman G.J., Bebenek I.G., Zeidler M. et al. HIF-1 expression is associated with CCL2 chemokine expression in airway inflammatory cells: implications in allergic airway inflammation // Respir. Res. 2012. V. 13. № 1. P. 60.
- 3. Bi Y., Tu Z., Zhang Y. et al. Identification of ALPPL2 as a naïve pluripotent state-specific surface protein essential for human naive pluripotency regulation // Cell Rep. 2020. V. 30. № 11. P. 3917–3931.e5.
- 4. Binó L., Kučera J., Štefková K. et al. The stabilization of hypoxia inducible factor modulates differentiation status and inhibits the proliferation of mouse embryonic stem cells // Chem. Biol. Interact. 2016. V. 244. P. 204–214.
- 5. Chan Y.-S., Göke J., Ng J.-H. et al. Induction of a human pluripotent state with distinct regulatory circuitry that resembles preimplantation epiblast // Cell Stem Cell. 2013. V. 13. № 6. P. 663–675.
- 6. Collier A.J., Rugg-Gunn P.J. Identifying human naïve pluripotent stem cells − evaluating state-specific reporter lines and cell-surface markers // BioEssays. 2018. V. 40. № 5. P. 1700239.
- 7. Cowan C.A., Klimanskaya I., McMahon J. et al. Derivation of embryonic stem-cell lines from human blastocysts // N. Engl. J. Med. 2004. V. 350. № 13. P. 1353–1356.
- 8. Dahéron L., Opitz S.L., Zaehres H. et al. LIF/STAT3 signaling fails to maintain self-renewal of human embryonic stem cells // Stem Cells. 2004. V. 22. № 5. P. 770–778.
- 9. Dunwoodie S.L. The role of hypoxia in development of the mammalian embryo // Dev. Cell. 2009. V. 17. № 6. P. 755–773.
- 10. Ezashi T., Das P., Roberts R.M. Low O2 tensions and the prevention of differentiation of hES cells // Proc. Natl. Acad. Sci. USA. 2005. V. 102. № 13. P. 4783–4788.
- 11. Forristal C.E., Wright K.L., Hanley N.A. et al. Hypoxia inducible factors regulate pluripotency and proliferation in human embryonic stem cells cultured at reduced oxygen tensions // Reproduction. 2009. V. 139. № 1. P. 85–97.
- 12. Forsyth N.R., Musio A., Vezzoni P. et al. Physiologic oxygen enhances human embryonic stem cell clonal recovery and reduces chromosomal abnormalities // Cloning Stem Cells. 2006. V. 8. № 1. P. 16–23.
- 13. Gafni O., Weinberger L., Mansour A.A. et al. Derivation of novel human ground state naive pluripotent stem cells // Nature. 2013. V. 504. № 7479. P. 282–286.
- 14. Gu M. Efficient differentiation of human pluripotent stem cells to endothelial cells // Curr. Protoc. Hum. Genet. 2018. V. 98. № 1. P. e64.
- 15. Guo G., von Meyenn F., Rostovskaya M. et al. Epigenetic resetting of human pluripotency // Development. 2017. V. 144. № 15. P. 2748–2763.
- 16. Hanna J., Cheng A.W., Saha K. et al. Human embryonic stem cells with biological and epigenetic characteristics similar to those of mouse ESCs // Proc. Natl. Acad. Sci. USA. 2010. V. 107. № 20. P. 9222–9227.
- 17. Hasegawa Y., Takahashi N., Forrest A.R.R. et al. CC chemokine ligand 2 and leukemia inhibitory factor cooperatively promote pluripotency in mouse induced pluripotent cells // Stem Cells. 2011. V. 29. № 8. P. 1196–1205.
- 18. Hasegawa Y., Tang D., Takahashi N. et al. CCL2 enhances pluripotency of human induced pluripotent stem cells by activating hypoxia related genes // Sci. Rep. 2014. V. 4. P. 5228.
- 19. Hashimoto T., Shibasaki F. Hypoxia-inducible factor as an angiogenic master switch // Front. Pediatr. 2015. V. 3. P. 33.
- 20. Hellemans J., Mortier G., De Paepe A. et al. qBase relative quantification framework and software for management and automated analysis of real-time quantitative PCR data // Genome Biol. 2008. V. 8. № 2. P. R19.
- 21. Isaja L., Mucci S., Vera J. et al. Chemical hypoxia induces apoptosis of human pluripotent stem cells by a NOXA-mediated HIF-1α and HIF-2α independent mechanism // Sci. Rep. 2020. V. 10. P. 20653.
- 22. Jeon E.S., Shin J.H., Hwang S.J. et al. Cobalt chloride induces neuronal differentiation of human mesenchymal stem cells through upregulation of microRNA-124a // Biochem. Biophys. Res. Commun. 2014. V. 444. № 4. P. 581–587.
- 23. Lengner C.J., Gimelbrant A.A., Erwin J.A. et al. Derivation of pre-X inactivation human embryonic stem cells under physiological oxygen concentrations // Cell. 2010. V. 141. № 5. P. 872–883.
- 24. Malakhova A.A., Grigor’eva E.V., Pavlova S.V. et al. Generation of induced pluripotent stem cell lines ICGi021-A and ICGi022-A from peripheral blood mononuclear cells of two healthy individuals from Siberian population // Stem Cell Res. 2020. V. 48. 101952.
- 25. Matsuda T., Nakamura T., Nakao K. et al. STAT3 activation is sufficient to maintain an undifferentiated state of mouse embryonic stem cells // EMBO J. 1999. V. 18. № 15. P. 4261–4269.
- 26. Messmer T., von Meyenn F., Savino A. et al. Transcriptional heterogeneity in naïve and primed human pluripotent stem cells at single-cell resolution // Cell Rep. 2019. V. 26. № 4. P. 815.
- 27. Mojsilovic-Petrovic J., Callaghan D., Cui H. et al. Hypoxia-inducible factor-1 (HIF-1) is involved in the regulation of hypoxia-stimulated expression of monocyte chemoattractant protein-1 (MCP-1/CCL2) and MCP-5 (Ccl12) in astrocytes // J. Neuroinflammation. 2007. V. 4. P. 12.
- 28. Nakamura T., Okamoto I., Sasaki K. et al. A developmental coordinate of pluripotency among mice, monkeys and humans // Nat. 2016. V. 537. № 7618. P. 57–62.
- 29. Närvä E., Pursiheimo J.-P., Laiho A. et al. Continuous hypoxic culturing of human embryonic stem cells enhances SSEA-3 and MYC levels // PLoS One. 2013. V. 8. № 11. P. e78847.
- 30. Ng K.M., Chan Y.C., Lee Y.K. et al. Cobalt chloride pretreatment promotes cardiac differentiation of human embryonic stem cells under atmospheric oxygen level // https://home.liebertpub.com/cell. 2011. V. 13. № 6. P. 527–537.
- 31. Podkalicka P., Stępniewski J., Mucha O. et al. Hypoxia as a driving force of pluripotent stem cell reprogramming and differentiation to endothelial cells // Biomolecules. 2020. V. 10. № 12. P. 1–30.
- 32. Salikhova D.I., Leonov G.E., Bukharova T.B. et al. Comparative analysis of the paracrine action of neuronal and glial progenitor cells derived from induced human pluripotent stem cells // Bull. Exp. Biol. Med. 2020. V. 169. № 1. P. 176–181.
- 33. Schödel J., Oikonomopoulos S., Ragoussis J. et al. High-resolution genome-wide mapping of HIF-binding sites by ChIP-seq // Blood. 2011. V. 117. № 23. P. e207–e217.
- 34. Skuli N., Liu L., Runge A. et al. Endothelial deletion of hypoxia-inducible factor–2α (HIF-2α) alters vascular function and tumor angiogenesis // Blood. 2009. V. 114. № 2. P. 469.
- 35. Sperber H., Mathieu J., Wang Y. et al. The metabolome regulates the epigenetic landscape during naive-to-primed human embryonic stem cell transition // Nat. Cell Biol. 2015. V. 17. № 12. P. 1523–1535.
- 36. Sugimoto K., Matsuura T., Nakazono A. et al. Effects of hypoxia inducible factors on pluripotency in human iPS cells // Microsc. Res. Tech. 2018. V. 81. № 7. P. 749–754.
- 37. Takashima Y., Guo G., Loos R. et al. Resetting transcription factor control circuitry toward ground-state pluripotency in human // Cell. 2014. V. 158. № 6. P. 1254–1269.
- 38. Theunissen T.W., Powell B.E., Wang H. et al. Systematic identification of culture conditions for induction and maintenance of naïve human pluripotency // Cell Stem Cell. 2014. V. 15. № 4. P. 471–487.
- 39. Vaskova E.A., Medvedev S.P., Sorokina A.E. et al. Transcriptome characteristics and X-chromosome inactivation status in cultured rat pluripotent stem cells // Stem Cells Dev. 2015. V. 24. № 24. P. 2912–2924.
- 40. Ware C.B., Nelson A.M., Mecham B. et al. Derivation of naive human embryonic stem cells // Proc. Natl. Acad. Sci. USA. 2014. V. 111. № 12. P. 4484–4489.
- 41. Zakharova I.S., Zhiven’ M.K., Saaya S.B. et al. Endothelial and smooth muscle cells derived from human cardiac explants demonstrate angiogenic potential and suitable for design of cell-containing vascular grafts // J. Transl. Med. 2017. V. 15. № 1. P. 54.
- 42. Zakharova I.S., Saaya S.B., Shevchenko A.I. et al. Mitomycin-treated endothelial and smooth muscle cells suitable for safe tissue engineering approaches // Front. Bioeng. Biotechnol. 2022. V. 10. P. 772981.
- 43. Zakharova I.S., Shevchenko A.I., Tmoyan N.A. et al. Induced pluripotent stem cell line ICGi036-A generated by reprogramming peripheral blood mononuclear cells from a patient with familial hypercholesterolemia caused due to compound heterozygous p.Ser177Leu/p.Cys352Arg mutations in LDLR // Stem Cell Res. 2022. V. 59. 102653.
- 44. Zhdanov A.V., Okkelman I.A., Collins FW.J. et al. A novel effect of DMOG on cell metabolism: direct inhibition of mitochondrial function precedes HIF target gene expression // Biochim. Biophys. Acta. 2015. V. 1847. № 10. P. 1254–1266.
- 45. Zudaire E., Gambardella L., Kurcz C., Vermeren S. A computational tool for quantitative analysis of vascular networks // PLoS One. 2011. V. 6. № 11. P. e27385.
