vestibИзвестия Национальной академии наук Беларуси. Серия биологических наукProceedings of the National Academy of Sciences of Belarus, Biological Series1029-89402524-230XThe Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1029-8940-2020-65-1-106-118vestib-655Research ArticleОБЗОРЫREVIEWSЭпигенетический контроль дифференцировки мезенхимальных стволовых клеток. Дифференцировка стволовых клеток в печениEpigenetic control of differentiation of mesenchymal stem cells. Stem cells differentiation in liverВолотовскийИ. Д.VolotovskiI. D.

Волотовский Игорь Дмитриевич – академик, д-р биол. наук, заведующий лабораторией

ул. Академическая, 27, 220072, г. Минск

Igor D. Volotovski – Academician, D. Sc. (Biol.), Head of the Labоratory

27, Akademicheskaya Str., 220072, Minsk

volotovski@yahoo.comЕрмоленкоД. А.ErmolenkoD. A.

Ермоленко Дарья Андреевна – мл. науч. сотрудник

ул. Академическая, 27, 220072, г. Минск

Darya A. Ermolenko – Junior researcher

27, Akademicheskaya Str., 220072, Minsk

ermolenko_darya94@gmail.ruГороховаН. И.HarokhavaN. I.

Горохова Надежда Игоревна – мл. науч. сотрудник

ул. Академическая, 27, 220072, г. Минск

Nadezhda I. Harokhava – Junior researcher

27, Akademicheskaya Str., 220072, Minsk

nadezhdanilina@gmail.comИнститут биофизики и клеточной инженерии НАН БеларусиInstitute of Biophysics and Cell Engineering of the National Academy of Sciences of Belarus202011022020651106118Copyright © Волотовский И.Д., Ермоленко Д.А., Горохова Н.И., 20202020Волотовский И.Д., Ермоленко Д.А., Горохова Н.И.Volotovski I.D., Ermolenko D.A., Harokhava N.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestibio.belnauka.by/jour/article/view/655

В обзоре приведены последние данные по эпигенетическому контролю дифференцировки мезенхимальных стволовых клеток, лежащего в основе эмбриогенеза и регенеративных процессов в организме. Эпигенетический контроль базируется на трех внутримолекулярных механизмах – метилировании ДНК, структурной модификации белков гистонов и действии микроРНК на посттранскрипционных и посттрансляционных уровнях. В качестве примера рассмотрены вопросы дифференцировки стволовых клеток в печени.

The recent data on epigenetic control of differentiation in mesenchymal stem cells to be the background of embryogenesis and regeneration process in organism are considered. Epigenetic control is bases on three intramolecular mechanisms – DNA methylation, structural modification of histone proteins and microRNA active on posttranscription and posttranslation levels. As an example, the issues of stem cell differentiation in the liver are considered.

мезенхимальные стволовые клеткидифференцировкаэпигенетикаметилирование ДНКструктурная модификация гистоновмикроРНКстволовые клетки печениmesenchymal stem cellsdifferentiationepigeneticsDNA methylationhistone structural modificationmicroRNAstem cells in liverReferencesEpigenetics / ed. : O. D. Allis [et al.]. – 2nd ed. – New York : Cold Spring Harbor Laboratory Press, 2015. – 984 p.Allis O. D., Caparras M., Jenuwein T., Reinberg D. (ed.). Epigenetics. New York, Cold Spring Harbor Laboratory Press, 2015. 984 p.Hoffmann, A. Molecular epigenetic switches in neurodevelopment in health and disease / A. Hoffmann, Ch. A. Zimmermann, D. Spengler // Front Behav. Neurosci. – 2015. – Vol. 9. – Art. 120. https://doi.org/10.3389/fnbeh.2015.00120Hoffmann A., Zimmermann C. A., Spengler D. Molecular epigenetic switches in neurodevelopment in health and disease. Frontiers in Behavioral Neuroscience, 2015, vol. 9, art. 120. https://doi.org/10.3389/fnbeh.2015.00120Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement / M. Dominici [et al.] // Cytotherapy. – 2006. – Vol. 8, N 4. – P. 315–317. https://doi.org/10.1080/14653240600855905Dominici M., Le Blanc K., Mueller I., Slaper-Cortenbach I., Marini F., Krause D. S., Deans R. J., Keating A., Prockop D. J., Horwitz E. M. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 2006, vol. 8, no. 4, pp. 315–317. https://doi.org/10.1080/14653240600855905Progress in mesenchymal stem cell-based therapy for acute liver failure / Y.-H. Wang [et al.] // Stem Cell Res. Ther. – 2018. – Vol. 9. – Art. 227. https://doi.org/10.1186/s13287-018-0972-4Wang Y.-H., Wu D.-B., Chen B., Chen E.-Q., Tang H. Progress in mesenchymal stem cell-based therapy for acute liver failure. Stem Cell Research and Therapy, 2018, vol. 9, no. 1, art. 227. https://doi.org/10.1186/s13287-018-0972-4Li, X. Epigenetic regulation of mammalian stem cells / X. Li, X. Zhao // Stem Cells Dev. – 2008. – Vol. 17, N 6. – P. 1043–1052. https://doi.org/10.1089/scd.2008.0036Li X., Zhao X. Epigenetic regulation of mammalian stem cells. Stem Cells and Development, 2008, vol. 17, no. 6, pp. 1043–1052. https://doi.org/10.1089/scd.2008.0036Epigenetic modulation of stem cells in neurodevelopment: the role of methylation and acetylation / M. Podobinska [et al.] // Front Cell Neurosci. – 2017. – Vol. 11, N 23. – Art. 23. https://doi.org/10.3389/fncel.2017.00023Podobinska M., Szablowska-Gadomska I., Augustyniak J., Sandvig I., Sandvig A., Buzanska, L. Epigenetic modulation of stem cells in neurodevelopment: the role of methylation and acetylation. Frontiers in Cellular Neuroscience, 2017, vol. 14, art. 23. https://doi.org/10.3389/fncel.2017.00023Epigenetic regulation of mesenchymal stem cells: a focus on osteogenic and adipogenic differentiation / C. M. Teven [et al.] // Stem Cells Int. – 2011. – Vol. 2011. – Art. ID 201231. https://doi.org/10.4061/2011/201371Teven C. M., Liu X., Hu N., Tang N., Kim S. H., Huang E. [et al.]. Epigenetic regulation of mesenchymal stem cells: a focus on osteogenic and adipogenic differentiation. Stem Cells International, 2011, vol. 2011, art. ID 201231. https://doi.org/10.4061/2011/201371The molecular hallmarks of epigenetic control / C. D. Alles, T. Jenuwein // Nat. Rev. Genetics. – 2016. – Vol. 17, N 8. – P. 487–500. https://doi.org/10.1038/nrg.2016.59Alles C. D., Jenuwein T. The molecular hallmarks of epigenetic control. Nature Reviews Genetics, 2016, vol. 17, no. 8, pp. 487–500. https://doi.org/10.1038/nrg.2016.59Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain / J. U. Guo [et al.] // Cell. – 2011. – Vol. 145, N 3. – P. 423–434. https://doi.org/10.1016/j.cell.2011.03.022Guo J. U., Su Y., Zhong C., Ming G., Song H. Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain. Cell, 2011, vol. 145, no. 3, pp. 423–434. https://doi.org/10.1016/j.cell.2011.03.022Moran-Salvador, E. Epigenetics and liver fibrosis / E. Moran-Salvador, J. Mann // Cell Mol. Gastroenterol. Hepatol. – 2017. – Vol. 4, N 1. – P. 125–134. https://doi.org/10.1016/j.jcmgh.2017.04.007Moran-Salvador E., Mann J. Epigenetics and liver fibrosis. Cellular and Molecular Gastroenterology and Hepatology, 2017, vol. 4, no. 1, pp. 125–134. https://doi.org/10.1016/j.jcmgh.2017.04.007Suganuma, T. Signals and combinatorial functions of histone modifications / T. Suganuma, J. L. Workman // Annu. Rev. Biochem. – 2011. – Vol. 80, N 1. – P. 473–499. https://doi.org/10.1146/annurev-biochem-061809-175347Suganuma T., Workman J. L. Signals and combinatorial functions of histone modifications. Annual Review of Biochemistry, 2011, vol. 80, no. 1, pp. 473–499. https://doi.org/10.1146/annurev-biochem-061809-175347Rothbart, S. B. Interpreting the language of histone and DNA modifications / S. B. Rothbart, B. D. Strahl // Biochim. Biophys. Acta. Gene Reg. Mech. – 2014. – Vol. 1839, N 8. – P. 627–643. https://doi.org/10.1016/j.bbagrm.2014.03.001Rothbart S. B., Strahl B. D. Interpreting the language of histone and DNA modifications. Biochimica et Biophysica Acta (BBA) – Gene Regulatory Mechanism, 2014, vol. 1839, no. 8, pp. 627–643. https://doi.org/10.1016/j.bbagrm.2014.03.001Jenuwein, T. Translating the histone code / T. Jenuwein, O. D. Allis // Science. – 2001. – Vol. 293, N 5532. – P. 1074–1080. https://doi.org/10.1126/science.1063127Jenuwein T., Allis O. D. Translating the histone code. Science, 2001, vol. 293, no. 5532, pp. 1074–1080. https://doi.org/10.1126/science.1063127Goldberg, A. D. Epigenetics: a landscape takes shape / A. D. Goldberg, C. D. Allis, E. Bernstein // Cell. – 2007. – Vol. 128, N 4. – P. 635–638. https://doi.org/10.1016/j.cell.2007.02.006Goldberg A. D., Allis C. D., Bernstein E. Epigenetics: a landscape takes shape. Cell, 2007, vol. 128, no. 4, pp. 635–638. https://doi.org/10.1016/j.cell.2007.02.006WERAM: a database of writers, erasers and readers of histone acetylation and methylation in eukaryotes / Y. Xu [et al.] // Nucl. Acids Res. – 2017. – Vol. 45, N D1. – P. D264–D270. https://doi.org/10.1093/nar/gkw1011Xu Y., Zhang S., Lin S., Guo Y., Deng W., Zhang Y., Xue Y. WERAM: a database of writers, erasers and readers of histone acetylation and methylation in eukaryotes. Nucleic Acids Research, 2016, vol. 45, no. D1, pp. D264–D270. https://doi.org/10.1093/nar/gkw1011New, M. HDAC inhibitor-based therapies: can we interpret the code? / M. New, H. Olzscha, N. B. La Thangue // Mol. Oncol. – 2012. – Vol. 6, N 6. – P. 637–656. https://doi.org/10.1016/j.molonc.2012.09.003New M., Olzscha H., La Thangue N. B. HDAC inhibitor-based therapies: Can we interpret the code? Molecular Oncology, 2012, vol. 6, no. 6, pp. 637–656. https://doi.org/10.1016/j.molonc.2012.09.003Moutinho C. MicroRNAs and epigenetics / C. Moutinho, M. Esteller // Advances in Cancer Research / ed. : C. M. Croce, P. B. Fishe. – London, 2017. – Vol. 135 : miRNA and Cancer. – P. 189–220.Moutinho C., Esteller M. MicroRNAs and epigenetics. Advances in Cancer Research. Vol. 135. miRNA and Cancer. London, 2017, pp. 189–220.MicroRNA-204 regulates Runx2 protein expression and mesenchymal progenitor cell differentiation / J. Huang [et al.] // Stem Cells. – 2010. – Vol. 28, N 2. – P. 357–364. https://doi.org/10.1002/stem.288Huang J., Zhao L., Xing L., Chen D. MicroRNA-204 regulates Runx2 protein expression and mesenchymal progenitor cell differentiation. Stem Cells, 2009, vol. 28, no. 2, pp. 357–364. https://doi.org/10.1002/stem.288Dykes, I. M. Transcriptional and post-transcriptional gene regulation by long non-coding RNA / I. M. Dykes, C. Emanueli // Genomics Proteomics Bioinformatics. – 2017. – Vol. 15, N 3. – P. 177–186. https://doi.org/10.1016/j.gpb.2016.12.005Dykes I. M., Emanueli C. Transcriptional and post-transcriptional gene regulation by long non-coding RNA. Genomics, Proteomics and Bioinformatics, 2017, vol. 15, no. 3, pp. 177–186. https://doi.org/10.1016/j.gpb.2016.12.005Fate decision of mesenchymal stem cells: adipocytes or osteoblasts? / Q. Chen [et al.] // Cell Death Differ. – 2016. – Vol. 23, N 7. – P. 1128–1139. https://doi.org/10.1038/cdd.2015.168Chen Q., Shou P., Zheng C., Jiang M., Cao G., Yang Q., Shi, Y. Fate decision of mesenchymal stem cells: adipocytes or osteoblasts? Cell Death and Differentiation, 2016, vol. 23, no. 7, pp. 1128–1139. https://doi.org/10.1038/cdd.2015.168Non-coding RNA / J. S. Mattick [et al.] // Hum. Mol. Genet. – 2006. – Vol. 15, suppl. 1. – P. R17–R29. https://doi.org/10.1093/hmg/ddl046Mattick J. S., Makunin I. V. Non-coding RNA. Human Molecular Genetics, 2006, vol. 15, suppl. 1, pp. R17–R29. https://doi.org/10.1093/hmg/ddl046Osteoporosis and the replacement of cell populations of the marrow by adipose tissue. A quantitative study of 84 iliac bone biopsies / P. Meunier [et al.] // Clin. Orthop. Relat. Res. – 1971. – Vol. 80. – P. 147–154. https://doi.org/10.1097/00003086-197110000-00021Meunier P., Aaron J., Edouard C., Vignon G. Osteoporosis and the replacement of cell populations of the marrow by adipose tissue. Clinical Orthopaedics and Related Research, 1971, vol. 80, pp. 147–154. https://doi.org/10.1097/00003086-197110000-00021Stem cells transplantation in the treatment of patients with liver failure / Y.-C. Tao [et al.] // Curr. Stem Cell Res. Ther. – 2018. – Vol. 13, N 3. – P. 193–201. https://doi.org/10.2174/1574888X13666180105123915Tao Y.-C., Wang M.-L., Chen E.-Q., Tang H. Stem cells transplantation in the treatment of patients with liver failure. Current Stem Cell Research and Therapy, 2018, vol. 13, no. 3, pp. 193–201. https://doi.org/10.2174/1574888X13666180105123915Miyajima, A. Stem/progenitor cells in liver development, homeostasis, regeneration, and reprogramming / A. Miyajima, M. Tanaka, T. Itoh // Cell Stem Cell. – 2014. – Vol. 14, N 5. – P. 561–574. https://doi.org/10.1016/j.stem.2014.04.010Miyajima A., Tanaka M., Itoh T. Stem/progenitor cells in liver development, homeostasis, regeneration, and reprogramming. Cell Stem Cell, 2014, vol. 14, no. 5, pp. 561–574. https://doi.org/10.1016/j.stem.2014.04.010Liver stem/progenitor cells: their characteristics and regulatory mechanisms / M. Tanaka [et al.] // J. Biochem. – 2011. – Vol. 149, N 3. – P. 231–239. https://doi.org/10.1093/jb/mvr001Tanaka M., Itoh T., Tanimizu N., Miyajima A. Liver stem/progenitor cells: their characteristics and regulatory mechanisms. Journal of Biochemistry, 2011, vol. 149, no. 3, pp. 231–239. https://doi.org/10.1093/jb/mvr001In vivo hepatic differentiation of mesenchymal stem cells from human umbilical cord blood after transplantation into mice with liver injury / J. Yu [et al.] // Biochem. Biophys. Res. Commun. – 2012. – Vol. 422, N 4. – P. 539–545. https://doi.org/10.1016/j.bbrc.2012.04.156Yu J., Cao H., Yang J., Pan Q., Ma J., Li J., Li Y., Li J., Wang Y., Li L. In vivo hepatic differentiation of mesenchymal stem cells from human umbilical cord blood after transplantation into mice with liver injury. Biochemical and Biophysical Research Communications, 2012, vol. 422, no. 4, pp. 539–545. https://doi.org/10.1016/j.bbrc.2012.04.156

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