Preliminary Exposure to Histone Deacetylase Inhibitors Changes the Direction of Human IPSCs Differentiation with the Formation of Cardiospheres Instead of Skin Organoids

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Abstract

Pluripotent stem cells (PSCs) are a unique cell type that can differentiate into all cell types in the body. In PSC culture, subpopulations with different levels of pluripotency may exist, which leads to different results during their differentiation. One of the key factors that determine the state of pluripotency and influence the differentiation potential of PSCs is the epigenetic state of cells, including the level of histone deacetylation. Activation of histone deacetylase (HDAC) in human and mouse PSCs increases the percentage of heterochromatin. In this work, we used a protocol for the differentiation of embryoid bodies from induced human pluripotent hIPSC cells, designed for the formation of ectoderm and neuroectoderm with their subsequent development into skin organoids. However, after hIPSCs were exposed to HDAC inhibitors (sodium butyrate and valproic acid), the direction of their differentiation changed: mesoderm was formed, which subsequently developed into contracting cardiospheres.

About the authors

V. K. Abdyev

Koltsov Institute of Developmental Biology of Russian Academy of Sciences

Author for correspondence.
Email: mailtovepa@gmail.com
Russia, 119334, Moscow

A. A. Riabinin

Koltsov Institute of Developmental Biology of Russian Academy of Sciences

Author for correspondence.
Email: andrey951233@mail.ru
Russia, 119334, Moscow

E. D. Erofeeva

Lomonosov Moscow State University, Faculty of Biology

Email: andrey951233@mail.ru
Russia, 119234, Moscow

M. D. Pankratova

Koltsov Institute of Developmental Biology of Russian Academy of Sciences; Lomonosov Moscow State University, Faculty of Biology

Email: andrey951233@mail.ru
Russia, 119334, Moscow; Russia, 119234, Moscow

E. A. Vorotelak

Koltsov Institute of Developmental Biology of Russian Academy of Sciences

Email: andrey951233@mail.ru
Russia, 119334, Moscow

A. V. Vasiliev

Koltsov Institute of Developmental Biology of Russian Academy of Sciences; Lomonosov Moscow State University, Faculty of Biology

Email: andrey951233@mail.ru
Russia, 119334, Moscow; Russia, 119234, Moscow

References

  1. Balafkan N., Mostafavi S., Schubert M. et al. A method for differentiating human induced pluripotent stem cells toward functional cardiomyocytes in 96-well microplates // Sci. Rep. 2020. V. 10. № 1. 18498. PMID: 33116175; PMCID: PMC7595118.https://doi.org/10.1038/s41598-020-73656-2
  2. Brons I., Smithers L.E., Trotter M.W.B. et al. Derivation of pluripotent epiblast stem cells from mammalian embryos // Nature. 2007. V. 448. № 7150. P. 191–195. https://doi.org/10.1038/nature05950
  3. Fischer B., Meier A., Dehne A. et al. A complete workflow for the differentiation and the dissociation of hiPSC-derived cardiospheres // Stem Cell Res. 2018. V. 32. P. 65–72. Epub 2018 Aug 24. PMID: 30218895. https://doi.org/10.1016/j.scr.2018.08.015
  4. Johnstone R.W. Histone-deacetylase inhibitors: novel drugs for the treatment of cancer // Nature. 2002. V. 1. № 4. P. 287–299. https://doi.org/10.1038/nrd772
  5. Lagarkova M.A., Eremeev A.V., Svetlakov A.V. et al. Human embryonic stem cell lines isolation, cultivation, and characterization // In Vitro Cell Dev. Biol. Anim. 2010. V. 46. № 3–4. P. 284–293. https://doi.org/10.1007/s11626-010-9282-6
  6. Lau K.X., Mason E.A., Kie J. et al. Unique properties of a subset of human pluripotent stem cells with high capacity for self-renewal // Nature Communications. 2020. V. 11. № 1. P. 1–18. https://doi.org/10.1038/s41467-020-16214-8
  7. Lee J., Koehler K.R. Skin organoids: A new human model for developmental and translational research // Exp. Dermatol. 2021. V. 30. № 4. P. 613–620. Epub 2021 Feb 18. PMID: 33507537; PMCID: PMC8265774.4).https://doi.org/10.1111/exd.14292
  8. Lee J., Rabbani C.C., Gao H. et al. Hair-bearing human skin generated entirely from pluripotent stem cells // Nature. 2020. V. 582. № 7812. P. 399–404.
  9. Saraiva N.Z., Oliveira C.S., Garcia J.M. Histone acetylation and its role in embryonic stem cell differentiation // World J. Stem. Cells. 2010. V. 2. № 6. P. 121–126. https://doi.org/10.4252/WJSC.V2.I6.121
  10. Seto E., Yoshida M. Erasers of histone acetylation: The histone deacetylase enzymes // Cold Spring Harb Perspect Biol. 2014. V. 6. № 4. a018713. https://doi.org/10.1101/CSHPERSPECT.A018713
  11. Shkumatov A., Baek K., Kong H. Matrix rigidity-modulated cardiovascular organoid formation from embryoid bodies // PLoS One. 2014. V. 14. № 9. 4 PMID: 24732893; PMCID: PMC3986240.https://doi.org/10.1371/journal.pone.0094764
  12. Takahashi K., Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors // Cell. 2006. V. 126. № 4. P. 663–676. https://doi.org/10.1016/j.cell.2006.07.024
  13. Teslaa T., Chaikovsky A.C., Lipchina I. et al. a-Ketoglutarate accelerates the initial differentiation of primed human pluripotent stem cells cell metabolism differentiation of primed human pluripotent stem cells // Cell Metabolism. 2016. V. 24. P. 485–493. https://doi.org/10.1016/j.cmet.2016.07.002
  14. Toyooka Y., Shimosato D., Murakami K. et al. Identification and characterization of subpopulations in undifferentiated ES cell culture // Development. 2008. V. 135. № 5. P. 909–918. https://doi.org/10.1242/DEV.017400
  15. Zhao M., Tang Y., Zhou Y., Zhang J. Deciphering role of wnt signalling in cardiac mesoderm and cardiomyocyte differentiation from human iPSCs: Four-dimensional control of Wnt pathway for hiPSC-CMs differentiation // Sci. Rep. 2019. V. 18. № 9. 1. PMID: 31852937; PMCID: PMC6920374.https://doi.org/10.1038/s41598-019-55620-x

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Copyright (c) 2023 В.К. Абдыев, А.А. Рябинин, Е.Д. Ерофеева, М.Д. Панкратова, Е.А. Воротеляк, А.В. Васильев