BMB Reports

생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
권호 표지
DOI QR코드

DOI QR Code

Mitochondrial genome mutations in mesenchymal stem cells derived from human dental induced pluripotent stem cells

  • Park, Jumi (Department of Convergence Medicine & Stem Cell Center, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Lee, Yeonmi (Department of Convergence Medicine & Stem Cell Center, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Shin, Joosung (Department of Convergence Medicine & Stem Cell Center, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Lee, Hyeon-Jeong (Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University) ;
  • Son, Young-Bum (Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University) ;
  • Park, Bong-Wook (Department of Dentistry, Gyeongsang National University School of Medicine, Institute of Health Science) ;
  • Kim, Deokhoon (Department of Pathology, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Rho, Gyu-Jin (Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University) ;
  • Kang, Eunju (Department of Convergence Medicine & Stem Cell Center, Asan Medical Center, University of Ulsan College of Medicine)
  • 투고 : 2019.02.13
  • 심사 : 2019.06.12
  • 발행 : 2019.12.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Ethical and safety issues have rendered mesenchymal stem cells (MSCs) popular candidates in regenerative medicine, but their therapeutic capacity is lower than that of induced pluripotent stem cells (iPSCs). This study compared original, dental tissue-derived MSCs with re-differentiated MSCs from iPSCs (iPS-MSCs). CD marker expression in iPS-MSCs was similar to original MSCs. iPS-MSCs expressed higher in pluripotent genes, but lower levels in mesodermal genes than MSCs. In addition, iPS-MSCs did not form teratomas. All iPSCs carried mtDNA mutations; some shared with original MSCs and others not previously detected therein. Shared mutations were synonymous, while novel mutations were non-synonymous or located on RNA-encoding genes. iPS-MSCs also harbored mtDNA mutations transmitted from iPSCs. Selected iPS-MSCs displayed lower mitochondrial respiration than original MSCs. In conclusion, screening for mtDNA mutations in iPSC lines for iPS-MSCs can identify mutation-free cell lines for therapeutic applications.

키워드

참고문헌

  1. Alan Trounson CM (2015) Stem cell therapies in clinical trials: progress and challenges. Cell Stem Cell 17, 11-22 https://doi.org/10.1016/j.stem.2015.06.007
  2. Moussavou G, Kwak DH, Lim MU et al (2013) Role of gangliosides in the differentiation of human mesenchymalderived stem cells into osteoblasts and neuronal cells. BMB Rep 46, 527-532 https://doi.org/10.5483/BMBRep.2013.46.11.179
  3. Zhao Q, Gregory CA, Lee RH et al (2015) MSCs derived from iPSCs with a modified protocol are tumor-tropic but have much less potential to promote tumors than bone marrow MSCs. Proc Natl Acad Sci U S A 112, 530-535 https://doi.org/10.1073/pnas.1423008112
  4. Kim C (2015) iPSC technology--Powerful hand for disease modeling and therapeutic screen. BMB Rep 48, 256-265 https://doi.org/10.5483/BMBRep.2015.48.5.100
  5. Zhao C and Ikeya M (2018) Generation and applications of induced pluripotent stem cell-derived mesenchymal stem cells. Stem Cells Int 2018, 9601623 https://doi.org/10.1155/2018/9601623
  6. Fukuta M, Nakai Y, Kirino K et al (2014) Derivation of mesenchymal stromal cells from pluripotent stem cells through a neural crest lineage using small molecule compounds with defined media. PLoS One 9, e112291 https://doi.org/10.1371/journal.pone.0112291
  7. Sheyn D, Ben-David S, Shapiro G et al (2016) Human induced pluripotent stem cells differentiate into functional mesenchymal stem cells and repair bone defects. Stem Cells Transl Med 5, 1447-1460 https://doi.org/10.5966/sctm.2015-0311
  8. Liang G and Zhang Y (2013) Genetic and epigenetic variations in iPSCs: potential causes and implications for application. Cell Stem Cell 13, 149-159 https://doi.org/10.1016/j.stem.2013.07.001
  9. Hamada M, Malureanu LA, Wijshake T, Zhou W and van Deursen JM (2012) Reprogramming to pluripotency can conceal somatic cell chromosomal instability. PLoS Genet 8, e1002913 https://doi.org/10.1371/journal.pgen.1002913
  10. Hussein SM, Batada NN, Vuoristo S et al (2011) Copy number variation and selection during reprogramming to pluripotency. Nature 471, 58-62 https://doi.org/10.1038/nature09871
  11. Gore A, Li Z, Fung HL et al (2011) Somatic coding mutations in human induced pluripotent stem cells. Nature 471, 63-67 https://doi.org/10.1038/nature09805
  12. Bar-Nur O, Russ HA, Efrat S and Benvenisty N (2011) Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet beta cells. Cell Stem Cell 9, 17-23 https://doi.org/10.1016/j.stem.2011.06.007
  13. Anguera MC, Sadreyev R, Zhang Z et al (2012) Molecular signatures of human induced pluripotent stem cells highlight sex differences and cancer genes. Cell Stem Cell 11, 75-90 https://doi.org/10.1016/j.stem.2012.03.008
  14. Son G and Han J (2018) Roles of mitochondria in neuronal development. BMB Rep 51, 549-556 https://doi.org/10.5483/BMBRep.2018.51.11.226
  15. Kim KM, Noh JH, Abdelmohsen K and Gorospe M (2017) Mitochondrial noncoding RNA transport. BMB Rep 50, 164-174 https://doi.org/10.5483/BMBRep.2017.50.4.013
  16. Wallace D (1994) Mitochondrial DNA sequence variation in human evolution and disease. Proc Natl Acad Sci U S A 91, 8739-8746 https://doi.org/10.1073/pnas.91.19.8739
  17. Kang E, Wang X, Tippner-Hedges R et al (2016) Age-related accumulation of somatic mitochondrial DNA mutations in adult-derived human iPSCs. Cell Stem Cell 18, 625-636 https://doi.org/10.1016/j.stem.2016.02.005
  18. Ma H, Folmes CD, Wu J et al (2015) Metabolic rescue in pluripotent cells from patients with mtDNA disease. Nature 524, 234-238 https://doi.org/10.1038/nature14546
  19. Diederichs S and Tuan RS (2014) Functional comparison of human-induced pluripotent stem cell-derived mesenchymal cells and bone marrow-derived mesenchymal stromal cells from the same donor. Stem Cells Dev 23, 1594-1610 https://doi.org/10.1089/scd.2013.0477
  20. Uccelli A, Moretta L and Pistoia V (2008) Mesenchymal stem cells in health and disease. Nat Rev Immunol 8, 726-736 https://doi.org/10.1038/nri2395
  21. Park BW, Kang EJ, Byun JH et al (2012) In vitro and in vivo osteogenesis of human mesenchymal stem cells derived from skin, bone marrow and dental follicle tissues. Differentiation 83, 249-259 https://doi.org/10.1016/j.diff.2012.02.008
  22. Moraes DA, Sibov TT, Pavon LF et al (2016) A reduction in CD90 (THY-1) expression results in increased differentiation of mesenchymal stromal cells. Stem Cell Res Ther 7, 97-016-0359-3
  23. Tsai C, Su P, Huang Y, Yew T and Hung S (2012) Oct4 and Nanog directly regulate Dnmt1 to maintain selfrenewal and undifferentiated state in mesenchymal stem cells. Mol cell 47, 169-182 https://doi.org/10.1016/j.molcel.2012.06.020
  24. Chen YS, Pelekanos RA, Ellis RL, Horne R, Wolvetang EJ and Fisk NM (2012) Small molecule mesengenic induction of human induced pluripotent stem cells to generate mesenchymal stem/stromal cells. Stem Cells Transl Med 1, 83-95 https://doi.org/10.5966/sctm.2011-0022
  25. Eto S, Goto M, Soga M et al (2018) Mesenchymal stem cells derived from human iPS cells via mesoderm and neuroepithelium have different features and therapeutic potentials. PLoS One 13, e0200790 https://doi.org/10.1371/journal.pone.0200790
  26. Frobel J, Hemeda H, Lenz M et al (2014) Epigenetic rejuvenation of mesenchymal stromal cells derived from induced pluripotent stem cells. Stem Cell Reports 3, 414-422 https://doi.org/10.1016/j.stemcr.2014.07.003
  27. Han SM, Han SH, Coh YR et al (2014) Enhanced proliferation and differentiation of Oct4- and Sox2- overexpressing human adipose tissue mesenchymal stem cells. Exp Mol Med 46, e101 https://doi.org/10.1038/emm.2014.28
  28. Takahashi K, Tanabe K, Ohnuki M et al (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861-872 https://doi.org/10.1016/j.cell.2007.11.019
  29. Prigione A, Fauler B, Lurz R, Lehrach H and Adjaye J (2010) The senescence-related mitochondrial/oxidative stress pathway is repressed in human induced pluripotent stem cells. Stem Cells 28, 721-733 https://doi.org/10.1002/stem.404
  30. Hill BG, Dranka BP, Zou L, Chatham JC and Darley-Usmar VM (2009) Importance of the bioenergetic reserve capacity in response to cardiomyocyte stress induced by 4-hydroxynonenal. Biochem. J 424, 99-107 https://doi.org/10.1042/BJ20090934
  31. Quax TE, Claassens NJ, Soll D and van der Oost J (2015) Codon bias as a means to fine-tune gene expression. Mol Cell 59, 149-161 https://doi.org/10.1016/j.molcel.2015.05.035
  32. Phillips NR, Sprouse ML and Roby RK (2014) Simultaneous quantification of mitochondrial DNA copy number and deletion ratio: a multiplex real-time PCR assay. Sci Rep 4, 3887 https://doi.org/10.1038/srep03887