Energy metabolism in nuclear reprogramming

Biomarkers in Medicine

Volumn 5, Issue 6, 2011, Pages 715-729

  Folmes, Clifford Dl ^a,b   Nelson, Timothy J ^a,b   Terzic, Andre ^a,b  

^a Marriott Heart Disease Research Program   (United States)

^b MAYO CLINIC   (United States)

Author keywords

biomarker; differentiation; glycolysis; induced pluripotent stem cell; metabolomics; metabotype; mitochondria; oxidative metabolism; regenerative medicine; stem cells

Indexed keywords

ADENOSINE TRIPHOSPHATE; BIOLOGICAL MARKER; MITOCHONDRIAL DNA; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE;

AEROBIC METABOLISM; ANAEROBIC CAPACITY; BIOENERGY; BIOGENESIS; BIOSYNTHESIS; CATABOLISM; CELL DIFFERENTIATION; CELL FATE; CELL LINEAGE; CELL MATURATION; CELL METABOLISM; CELL NUCLEUS; CELLULAR DISTRIBUTION; EMBRYONIC STEM CELL; ENERGY METABOLISM; GLYCOLYSIS; HIGH THROUGHPUT SCREENING; HUMAN; METABOLIC REGULATION; METABOLOMICS; MITOCHONDRIAL MEMBRANE POTENTIAL; MITOCHONDRIAL RESPIRATION; MOLECULAR BIOLOGY; MOLECULAR DYNAMICS; MOLECULAR GENETICS; NONHUMAN; NUCLEAR REPROGRAMMING; OXYGEN CONSUMPTION; PLURIPOTENT STEM CELL; PROTEIN MODIFICATION; REGULATOR GENE; REVIEW;

BIOLOGICAL MARKERS; ENERGY METABOLISM; GLYCOLYSIS; HUMANS; INDUCED PLURIPOTENT STEM CELLS; METABOLOMICS; MITOCHONDRIA; NUCLEAR REPROGRAMMING;

EID: 82755195582     PISSN: 17520363     EISSN: 17520371     Source Type: Journal    
DOI: 10.2217/bmm.11.87     Document Type: Review

References (119)

1. Terzic A, Folmes CD, Martinez-Fernandez A, Behfar A. Regenerative medicine. on the vanguard of health care. Mayo Clin. Proc. 86(7), 600-602 (2011).
2. Nelson TJ, Behfar A, Yamada S, Martinez-Fernandez A, Terzic A. Stem cell platforms for regenerative medicine. Clin. Transl. Sci. 2(3), 222-227 (2009).
3. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4), 663-676 (2006). (Pubitemid 44233629)
4. Nelson TJ, Terzic A. Induced pluripotent stem cells: an emerging theranostics platform. Clin. Pharmacol. Ther. 89(5), 648-650 (2011).
5. Dzeja PP, Terzic A. Phosphotransfer networks and cellular energetics. J. Exp. Biol. 206(Pt 12), 2039-2047 (2003). (Pubitemid 36761807)
6. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect. The metabolic requirements of cell proliferation. Science 324(5930), 1029-1033 (2009).
7. Gatenby RA, Gillies RJ. Why do cancers have high aerobic glycolysis? Nat. Rev. Cancer 4(11), 891-899 (2004). (Pubitemid 39472955)
8. Yu J, Vodyanik MA, Smuga-Otto K et al. Induced pluripotent stem cell lines derived from human somatic cells. Science 318(5858), 1917-1920 (2007).
9. Wernig M, Meissner A, Foreman R et al. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 448(7151), 318-324 (2007). (Pubitemid 47080337)
10. Gonzalez F, Boue S, Izpisua Belmonte JC. Methods for making induced pluripotent stem cells: reprogramming a la carte. Nat. Rev. Genet. 12(4), 231-242 (2011).
11. Lowry WE, Richter L, Yachechko R et al. Generation of human induced pluripotent stem cells from dermal fibroblasts. Proc. Natl Acad. Sci. USA 105(8), 2883-2888 (2008). (Pubitemid 351723638)
12. Mikkelsen TS, Hanna J, Zhang X et al. Dissecting direct reprogramming through integrative genomic analysis. Nature 454(7200), 49-55 (2008). (Pubitemid 351931978)
13. Meissner A, Wernig M, Jaenisch R. Direct reprogramming of genetically unmodified fibroblasts into pluripotent stem cells. Nat. Biotechnol. 25(10), 1177-1181 (2007). (Pubitemid 47538112)
14. Okita K, Ichisaka T, Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature 448(7151), 313-317 (2007). (Pubitemid 47080336)
15. Maherali N, Hochedlinger K. Guidelines and techniques for the generation of induced pluripotent stem cells. Cell Stem Cell 3(6), 595-605 (2008).
16. Martinez-Fernandez A, Nelson TJ, Yamada S et al. iPS programmed without c-MYC yield proficient cardiogenesis for functional heart chimerism. Circ. Res. 105(7), 648-656 (2009).
17. Nelson TJ, Martinez-Fernandez A, Yamada S, Perez-Terzic C, Ikeda Y, Terzic A. Repair of acute myocardial infarction by human stemness factors induced pluripotent stem cells. Circulation 120(5), 408-416 (2009).
18. Wernig M, Zhao JP, Pruszak J et al. Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease. Proc. Natl Acad. Sci. USA 105(15), 5856-5861 (2008). (Pubitemid 351758462)
19. Nelson TJ, Martinez-Fernandez A, Yamada S, Mael AA, Terzic A, Ikeda Y. Induced pluripotent reprogramming from promiscuous human stemness-related factors. Clin. Transl. Sci. 2(2), 118-126 (2009).
20. Folmes CD, Nelson TJ, Martinez-Fernandez A et al. Somatic oxidative bioenergetics transitions into pluripotency-dependent glycolysis to facilitate nuclear reprogramming. Cell Metab. 14(2), 264-271 (2011).
21. Panopoulos AD, Izpisua Belmonte JC. Anaerobicizing into pluripotency. Cell Metab. 14(2), 143-144 (2011).
22. Westermann B. Mitochondrial fusion and fission in cell life and death. Nat. Rev. Mol. Cell Biol. 11(12), 872-884 (2010).
23. Zeuschner D, Mildner K, Zaehres H, Scholer HR. Induced pluripotent stem cells at nanoscale. Stem Cells Dev. 19(5), 615-620 (2010).
24. Prigione A, Fauler B, Lurz R, Lehrach H, Adjaye J. The senescence-related mitochondrial/oxidative stress pathway is repressed in human induced pluripotent stem cells. Stem Cells 28(4), 721-733 (2010).
25. Suhr ST, Chang EA, Tjong J et al. Mitochondrial rejuvenation after induced pluripotency. PLoS One 5(11), e14095 (2010).
26. Varum S, Rodrigues AS, Moura Mb et al. Energy metabolism in human pluripotent stem cells and their differentiated counterparts. PLoS One 6(6), e20914 (2011).
27. Armstrong L, Tilgner K, Saretzki G et al. Human induced pluripotent stem cell lines show similar stress defense mechanisms and mitochondrial regulation to human embryonic stem cells. Stem Cells 28(4), 661-673 (2010).
28. Prigione A, Lichtner B, Kuhl H et al. Human iPSCs harbor homoplasmic and heteroplasmic mitochondrial DNA mutations while maintaining hESC-like metabolic reprogramming. Stem Cells 29(9), 1338-1348 (2011).
29. Hussein SM, Batada NN, Vuoristo S et al. Copy number variation and selection during reprogramming to pluripotency. Nature 471(7336), 58-62 (2011).
30. Lister R, Pelizzola M, Kida YS et al. Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature 471(7336), 68-73 (2011).
31. Gore A, Li Z, Fung Hl et al. Somatic coding mutations in human induced pluripotent stem cells. Nature 471(7336), 63-67 (2011).
32. Mummery C. Induced pluripotent stem cells -a cautionary note. N. Engl. J. Med. 364(22), 2160-2162 (2011).
33. Batten BE, Albertini DF, Ducibella T. Patterns of organelle distribution in mouse embryos during preimplantation development. Am. J. Anat. 178(2), 204-213 (1987). (Pubitemid 17031686)
34. Lonergan T, Bavister B, Brenner C. Mitochondria in stem cells. Mitochondrion 7(5), 289-296 (2007). (Pubitemid 47300173)
35. Rehman J. Empowering self-renewal and differentiation: the role of mitochondria in stem cells. J. Mol. Med. (Berlin) 88(10), 981-986 (2010).
36. Facucho-Oliveira JM, St John JC. The relationship between pluripotency and mitochondrial DNA proliferation during early embryo development and embryonic stem cell differentiation. Stem Cell Rev. Rep. 5(2), 140-158 (2009).
37. Chung S, Dzeja PP, Faustino RS, Perez-Terzic C, Behfar A, Terzic A. Mitochondrial oxidative metabolism is required for the cardiac differentiation of stem cells. Nat. Clin. Pract. Cardiovasc. Med. 4(Suppl. 1), S60-S67 (2007). (Pubitemid 46151906)
38. Baharvand H, Matthaei KI. The ultrastructure of mouse embryonic stem cells. Reprod. Biomed. Online 7(3), 330-335 (2003). (Pubitemid 37259288)
39. Baharvand H, Piryaei A, Rohani R, Taei A, Heidari MH, Hosseini A. Ultrastructural comparison of developing mouse embryonic stem cell and in vivo derived cardiomyocytes. Cell Biol. Int. 30(10), 800-807 (2006). (Pubitemid 44573859)
40. Cho YM, Kwon S, Pak YK et al. Dynamic changes in mitochondrial biogenesis and antioxidant enzymes during the spontaneous differentiation of human embryonic stem cells. Biochem. Biophys. Res. Commun. 348(4), 1472-1478 (2006). (Pubitemid 44291363)
41. St John JC, Ramalho-Santos J, Gray HL et al. The expression of mitochondrial DNA transcription factors during early cardiomyocyte in vitro differentiation from human embryonic stem cells. Cloning Stem Cells 7(3), 141-153 (2005). (Pubitemid 43150270)
42. Oh SK, Kim HS, Ahn HJ et al. Derivation and characterization of new human embryonic stem cell lines. SNUhES1, SNUhES2, and SNUhES3. Stem Cells 23(2), 211-219 (2005).
43. Facucho-Oliveira JM, Alderson J, Spikings EC, Egginton S, St John JC. Mitochondrial DNA replication during differentiation of murine embryonic stem cells. J. Cell Sci. 120(Pt. 22), 4025-4034 (2007). (Pubitemid 350269408)
44. Chung S, Arrell DK, Faustino RS, Terzic A, Dzeja PP. Glycolytic network restructuring integral to the energetics of embryonic stem cell cardiac differentiation. J. Mol. Cell. Cardiol. 48(4), 725-734 (2010).
45. Piccoli C, Ria R, Scrima R et al. Characterization of mitochondrial and extra-mitochondrial oxygen consuming reactions in human hematopoietic stem cells. Novel evidence of the occurrence of NAD(P) H oxidase activity. J. Biol. Chem. 280(28), 26467-26476 (2005). (Pubitemid 41022243)
46. Chen CT, Shih YR, Kuo TK, Lee OK, Wei YH. Coordinated changes of mitochondrial biogenesis and antioxidant enzymes during osteogenic differentiation of human mesenchymal stem cells. Stem Cells 26(4), 960-968 (2008).
47. Passos JF, Saretzki G, Ahmed S et al. Mitochondrial dysfunction accounts for the stochastic heterogeneity in telomere-dependent senescence. PLoS Biol. 5(5), e110 (2007).
48. Marion RM, Strati K, Li H et al. Telomeres acquire embryonic stem cell characteristics in induced pluripotent stem cells. Cell Stem Cell 4(2), 141-154 (2009).
49. Chin MH, Mason MJ, Xie W et al. Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures. Cell Stem Cell 5(1), 111-123 (2009).
50. Prigione A, Adjaye J. Modulation of mitochondrial biogenesis and bioenergetic metabolism upon in vitro and in vivo differentiation of human ES and iPS cells. Int. J. Dev. Biol. 54(11-12), 1729-1741 (2010).
51. Mathupala SP, Ko YH, Pedersen PL. The pivotal roles of mitochondria in cancer: Warburg and beyond and encouraging prospects for effective therapies. Biochim. Biophys. Acta 1797(6-7), 1225-1230 (2010).
52. Arora KK, Pedersen PL. Functional significance of mitochondrial bound hexokinase in tumor cell metabolism. Evidence for preferential phosphorylation of glucose by intramitochondrially generated ATP. J. Biol. Chem. 263(33), 17422-17428 (1988). (Pubitemid 19029327)
53. Bustamante E, Morris HP, Pedersen PL. Energy metabolism of tumor cells. Requirement for a form of hexokinase with a propensity for mitochondrial binding. J. Biol. Chem. 256(16), 8699-8704 (1981). (Pubitemid 12254812)
54. Bustamante E, Pedersen PL. High aerobic glycolysis of rat hepatoma cells in culture. Role of mitochondrial hexokinase. Proc. Natl Acad. Sci. USA 74(9), 3735-3739 (1977). (Pubitemid 8189957)
55. Ko YH, Pedersen PL, Geschwind JF. Glucose catabolism in the rabbit VX2 tumor model for liver cancer. Characterization and targeting hexokinase. Cancer Lett. 173(1), 83-91 (2001). (Pubitemid 32907513)
56. Pereira DA Silva AP, El-Bacha T, Kyaw N et al. Inhibition of energy-producing pathways of HepG2 cells by 3-bromopyruvate. Biochem. J. 417(3), 717-726 (2009).
57. Sugden MC, Holness MJ. Mechanisms underlying regulation of the expression and activities of the mammalian pyruvate dehydrogenase kinases. Arch. Physiol. Biochem. 112(3), 139-149 (2006). (Pubitemid 44871041)
58. Deberardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB. The biology of cancer. metabolic reprogramming fuels cell growth and proliferation. Cell Metab. 7(1), 11-20 (2008).
59. Warburg O. On the origin of cancer cells. Science 123(3191), 309-314 (1956).
60. Guppy M, Greiner E, Brand K. The role of the Crabtree effect and an endogenous fuel in the energy metabolism of resting and proliferating thymocytes. Eur. J. Biochem. 212(1), 95-99 (1993). (Pubitemid 23064604)
61. Christofk HR, Vander Heiden MG, Harris MH et al. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 452(7184), 230-233 (2008). (Pubitemid 351380249)
62. Pfeiffer T, Schuster S, Bonhoeffer S. Cooperation and competition in the evolution of ATP-producing pathways. Science 292(5516), 504-507 (2001). (Pubitemid 32335953)
63. Shaw RJ, Kosmatka M, Bardeesy N et al. The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress. Proc. Natl Acad. Sci. USA 101(10), 3329-3335 (2004). (Pubitemid 38338195)
64. Lum JJ, Bauer DE, Kong M et al. Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell 120(2), 237-248 (2005). (Pubitemid 40174766)
65. Deberardinis RJ, Mancuso A, Daikhin E et al. Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc. Natl Acad. Sci. USA 104(49), 19345-19350 (2007).
66. Hatzivassiliou G, Zhao F, Bauer De et al. ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell 8(4), 311-321 (2005). (Pubitemid 41443416)
67. Wellen KE, Hatzivassiliou G, Sachdeva UM, Bui TV, Cross JR, Thompson CB. ATP-citrate lyase links cellular metabolism to histone acetylation. Science 324(5930), 1076-1080 (2009).
68. Choudhary C, Kumar C, Gnad F et al. Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325(5942), 834-840 (2009).
69. Huangfu D, Maehr R, Guo W et al. Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat. Biotechnol. 26(7), 795-797 (2008). (Pubitemid 351961456)
70. Huangfu D, Osafune K, Maehr R et al. Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2. Nat. Biotechnol. 26(11), 1269-1275 (2008).
71. Liang G, Taranova O, Xia K, Zhang Y. Butyrate promotes induced pluripotent stem cell generation. J. Biol. Chem. 285(33), 25516-25521 (2010).
72. Mali P, Chou BK, Yen J et al. Butyrate greatly enhances derivation of human induced pluripotent stem cells by promoting epigenetic remodeling and the expression of pluripotency-associated genes. Stem Cells 28(4), 713-720 (2010).
73. Friis RM, Wu BP, Reinke SN, Hockman DJ, Sykes BD, Schultz MC. A glycolytic burst drives glucose induction of global histone acetylation by picNuA4 and SAGA. Nucleic Acids Res. 37(12), 3969-3980 (2009).
74. Cai L, Sutter BM, Li B, Tu BP. Acetyl-CoA induces cell growth and proliferation by promoting the acetylation of histones at growth genes. Mol. Cell 42(4), 426-437 (2011).
75. Kondoh H, Lleonart ME, Gil J et al. Glycolytic enzymes can modulate cellular life span. Cancer Res. 65(1), 177-185 (2005). (Pubitemid 40070808)
76. Yoshida Y, Takahashi K, Okita K, Ichisaka T, Yamanaka S. Hypoxia enhances the generation of induced pluripotent stem cells. Cell Stem Cell 5(3), 237-241 (2009).
77. Ezashi T, Das P, Roberts RM. Low O2 tensions and the prevention of differentiation of hES cells. Proc. Natl Acad. Sci. USA 102(13), 4783-4788 (2005). (Pubitemid 40471531)
78. Powers DE, Millman JR, Huang RB, Colton CK. Effects of oxygen on mouse embryonic stem cell growth, phenotype retention, and cellular energetics. Biotechnol. Bioeng. 101(2), 241-254 (2008).
79. Westfall SD, Sachdev S, Das P et al. Identification of oxygen-sensitive transcriptional programs in human embryonic stem cells. Stem Cells Dev. 17(5), 869-881 (2008).
80. Mohyeldin A, Garzon-Muvdi T, Quinones-Hinojosa A. Oxygen in stem cell biology. A critical component of the stem cell niche. Cell Stem Cell 7(2), 150-161 (2010).
81. Bensaad K, Tsuruta A, Selak MA et al. TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell 126(1), 107-120 (2006). (Pubitemid 44040989)
82. Banito A, Rashid ST, Acosta JC et al. Senescence impairs successful reprogramming to pluripotent stem cells. Genes Dev. 23(18), 2134-2139 (2009).
83. Hong H, Takahashi K, Ichisaka T et al. Suppression of induced pluripotent stem cell generation by the p53-p21 pathway. Nature 460(7259), 1132-1135 (2009).
84. Kawamura T, Suzuki J, Wang YV et al. Linking the p53 tumour suppressor pathway to somatic cell reprogramming. Nature 460(7259), 1140-1144 (2009).
85. Li H, Collado M, Villasante A et al. The Ink4/Arf locus is a barrier for iPS cell reprogramming. Nature 460(7259), 1136-1139 (2009).
86. Marion RM, Strati K, Li H et al. A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity. Nature 460(7259), 1149-1153 (2009).
87. Zhu S, Li W, Zhou H et al. Reprogramming of human primary somatic cells by OCT4 and chemical compounds. Cell Stem Cell 7(6), 651-655 (2010).
88. Chung S, Dzeja PP, Faustino RS, Terzic A. Developmental restructuring of the creatine kinase system integrates mitochondrial energetics with stem cell cardiogenesis. Ann. NY Acad. Sci. 1147, 254-263 (2008).
89. Perez-Terzic C, Behfar A, Mery A, Van Deursen JM, Terzic A, Puceat M. Structural adaptation of the nuclear pore complex in stem cell-derived cardiomyocytes. Circ. Res. 92(4), 444-452 (2003). (Pubitemid 36298205)
90. Perez-Terzic C, Faustino RS, Boorsma BJ et al. Stem cells transform into a cardiac phenotype with remodeling of the nuclear transport machinery. Nat. Clin. Pract. Cardiovasc. Med. 4(Suppl. 1), S68-S76 (2007). (Pubitemid 46151907)
91. Lonergan T, Brenner C, Bavister B. Differentiation-related changes in mitochondrial properties as indicators of stem cell competence. J. Cell. Physiol. 208(1), 149-153 (2006). (Pubitemid 43848999)
92. Schieke SM, Ma M, Cao L et al. Mitochondrial metabolism modulates differentiation and teratoma formation capacity in mouse embryonic stem cells. J. Biol. Chem. 283(42), 28506-28512 (2008).
93. Spitkovsky D, Sasse P, Kolossov E et al. Activity of complex III of the mitochondrial electron transport chain is essential for early heart muscle cell differentiation. FASEB J. 18(11), 1300-1302 (2004). (Pubitemid 39561583)
94. Kondoh H, Lleonart ME, Nakashima Y et al. A high glycolytic flux supports the proliferative potential of murine embryonic stem cells. Antioxid. Redox. Signal. 9(3), 293-299 (2007). (Pubitemid 46145978)
95. Dzeja PP, Chung S, Faustino RS, Behfar A, Terzic A. Developmental enhancement of adenylate kinase-AMPK metabolic signaling axis supports stem cell cardiac differentiation. PLoS One 6(4), e19300 (2011).
96. Varum S, Momcilovic O, Castro C, Ben-Yehudah A, Ramalho-Santos J, Navara CS. Enhancement of human embryonic stem cell pluripotency through inhibition of the mitochondrial respiratory chain. Stem Cell Res. 3(2-3), 142-156 (2009).
97. Arrell DK, Terzic A. Network systems biology for drug discovery. Clin. Pharmacol. Ther. 88(1), 120-125 (2010).
98. Faustino RS, Chiriac A, Niederlander NJ et al. Decoded calreticulin-deficient embryonic stem cell transcriptome resolves latent cardiophenotype. Stem Cells 28(7), 1281-1291 (2010).
99. Nicholson JK, Lindon JC, Holmes E. 'Metabonomics'. Understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica 29(11), 1181-1189 (1999).
100. Fiehn O. Metabolomics: the link between genotypes and phenotypes. Plant Mol. Biol. 48(1-2), 155-171 (2002).
101. Nicholson JK, Lindon JC. Systems biology. Metabonomics. Nature 455(7216), 1054-1056 (2008).
102. Cezar GG, Quam JA, Smith Am et al. Identification of small molecules from human embryonic stem cells using metabolomics. Stem Cells Dev. 16(6), 869-882 (2007).
103. Lindon JC, Nicholson JK. Spectroscopic and statistical techniques for information recovery in metabonomics and metabolomics. Ann. Rev. Anal. Chem. (Palo Alto Calif.) 1, 45-69 (2008).
104. Lei Z, Huhman DV, Sumner LW. Mass spectrometry strategies in metabolomics. J. Biol. Chem. 286(29), 25435-25442 (2011).
105. Weckwerth W. Metabolomics. An integral technique in systems biology. Bioanalysis 2(4), 829-836 (2010).
106. Griffiths WJ, Koal T, Wang Y, Kohl M, Enot DP, Deigner HP. Targeted metabolomics for biomarker discovery. Angew. Chem. Int. Ed. Engl. 49(32), 5426-5445 (2010).
107. Allen J, Davey HM, Broadhurst D et al. High-throughput classification of yeast mutants for functional genomics using metabolic footprinting. Nat. Biotechnol. 21(6), 692-696 (2003). (Pubitemid 36638098)
108. Ellis DI, Dunn WB, Griffin JL, Allwood JW, Goodacre R. Metabolic fingerprinting as a diagnostic tool. Pharmacogenomics 8(9), 1243-1266 (2007). (Pubitemid 47578232)
109. Kell DB, Brown M, Davey HM, Dunn WB, Spasic I, Oliver SG. Metabolic footprinting and systems biology. The medium is the message. Nat. Rev. Microbiol. 3(7), 557-565 (2005). (Pubitemid 40908875)
110. Jansen JF, Shamblott MJ, Van Zijl PC et al. Stem cell profiling by nuclear magnetic resonance spectroscopy. Magn. Reson. Med. 56(3), 666-670 (2006). (Pubitemid 44338887)
111. Turner WS, Seagle C, Galanko JA et al. Nuclear magnetic resonance metabolomic footprinting of human hepatic stem cells and hepatoblasts cultured in hyaluronan-matrix hydrogels. Stem Cells 26(6), 1547-1555 (2008).
112. Wang J, Alexander P, Wu L, Hammer R, Cleaver O, Mcknight SL. Dependence of mouse embryonic stem cells on threonine catabolism. Science 325(5939), 435-439 (2009).
113. Yanes O, Clark J, Wong DM et al. Metabolic oxidation regulates embryonic stem cell differentiation. Nat. Chem. Biol. 6(6), 411-417 (2010).
114. Wilding M, Dale B, Marino M et al. Mitochondrial aggregation patterns and activity in human oocytes and preimplantation embryos. Hum. Reprod. 16(5), 909-917 (2001). (Pubitemid 32451826)
115. Im CN, Kang NY, Ha HH et al. A fluorescent rosamine compound selectively stains pluripotent stem cells. Angew. Chem. Int. Ed. Engl. 49(41), 7497-7500 (2010).
116. Kang NY, Yun SW, Ha HH, Park SJ, Chang YT. Embryonic and induced pluripotent stem cell staining and sorting with the live-cell fluorescence imaging probe CDy1. Nat. Protoc. 6(7), 1044-1052 (2011).
117. Cezar GG, Donley EL. Stemina biomarker discovery. Regen. Med. 3(5), 665-669 (2008).
118. West PR, Weir AM, Smith AM, Donley EL, Cezar GG. Predicting human developmental toxicity of pharmaceuticals using human embryonic stem cells and metabolomics. Toxicol. Appl. Pharmacol. 247(1), 18-27 (2010).
119. Macintyre DA, Melguizo Sanchis D, Jimenez B, Moreno R, Stojkovic M, Pineda-Lucena A. Characterisation of human embryonic stem cells conditioning media by 1H-nuclear magnetic resonance spectroscopy. PLoS One 6(2), e16732 (2011).