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http://dx.doi.org/10.5483/BMBRep.2019.52.12.045

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)
Publication Information
BMB Reports / v.52, no.12, 2019 , pp. 689-694 More about this Journal
Abstract
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.
Keywords
hiPSCs; iPSC-derived MSCs; Mitochondrial DNA; Mutations; Regenerative medicine;
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Times Cited By KSCI : 2  (Citation Analysis)
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1 Alan Trounson CM (2015) Stem cell therapies in clinical trials: progress and challenges. Cell Stem Cell 17, 11-22   DOI
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   DOI
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   DOI
4 Kim C (2015) iPSC technology--Powerful hand for disease modeling and therapeutic screen. BMB Rep 48, 256-265   DOI
5 Zhao C and Ikeya M (2018) Generation and applications of induced pluripotent stem cell-derived mesenchymal stem cells. Stem Cells Int 2018, 9601623   DOI
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   DOI
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   DOI
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   DOI
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   DOI
10 Hussein SM, Batada NN, Vuoristo S et al (2011) Copy number variation and selection during reprogramming to pluripotency. Nature 471, 58-62   DOI
11 Gore A, Li Z, Fung HL et al (2011) Somatic coding mutations in human induced pluripotent stem cells. Nature 471, 63-67   DOI
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   DOI
13 Ma H, Folmes CD, Wu J et al (2015) Metabolic rescue in pluripotent cells from patients with mtDNA disease. Nature 524, 234-238   DOI
14 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   DOI
15 Son G and Han J (2018) Roles of mitochondria in neuronal development. BMB Rep 51, 549-556   DOI
16 Kim KM, Noh JH, Abdelmohsen K and Gorospe M (2017) Mitochondrial noncoding RNA transport. BMB Rep 50, 164-174   DOI
17 Wallace D (1994) Mitochondrial DNA sequence variation in human evolution and disease. Proc Natl Acad Sci U S A 91, 8739-8746   DOI
18 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   DOI
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   DOI
20 Uccelli A, Moretta L and Pistoia V (2008) Mesenchymal stem cells in health and disease. Nat Rev Immunol 8, 726-736   DOI
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   DOI
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 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   DOI
24 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   DOI
25 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   DOI
26 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   DOI
27 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   DOI
28 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   DOI
29 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   DOI
30 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   DOI
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   DOI
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   DOI