Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells

Nature

Volumn 518, Issue 7539, 2015, Pages 413-416

  Carey, Bryce W ^a   Finley, Lydia W S ^b   Cross, Justin R ^b   Allis, C David ^a   Thompson, Craig B ^b  

^a ROCKEFELLER UNIVERSITY   (United States)

^b MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 OXOGLUTARIC ACID; GLUCOSE; GLUTAMIC ACID; GLUTAMINE; SUCCINIC ACID; ALPHA-KETOGLUTARIC ACID; CHROMATIN; HISTONE;

AMINO ACID SYNTHESIS; ANIMAL CELL; ARTICLE; CARBON SOURCE; CATABOLISM; CELL DIFFERENTIATION; CELL METABOLISM; CELL PLURIPOTENCY; CELL RENEWAL; CELLULAR, SUBCELLULAR AND MOLECULAR BIOLOGICAL PHENOMENA AND FUNCTIONS; CHROMATIN; CITRIC ACID CYCLE; DNA METHYLATION; EMBRYO; EMBRYONIC STEM CELL; HISTONE DEMETHYLATION; IN VITRO STUDY; METABOLITE; MOUSE; NONHUMAN; PLURIPOTENT STEM CELL; PRIORITY JOURNAL; REGULATORY MECHANISM; ANIMAL; CELL LINE; CELL MEMBRANE PERMEABILITY; CELL PROLIFERATION; CYTOLOGY; DRUG EFFECTS; GENETIC EPIGENESIS; GENETIC TRANSCRIPTION; GENETICS; INTRACELLULAR SPACE; METABOLISM; METHYLATION;

ANIMALS; CELL DIFFERENTIATION; CELL LINE; CELL MEMBRANE PERMEABILITY; CELL PROLIFERATION; CHROMATIN; DNA METHYLATION; EMBRYONIC STEM CELLS; EPIGENESIS, GENETIC; GLUCOSE; GLUTAMIC ACID; HISTONES; INTRACELLULAR SPACE; KETOGLUTARIC ACIDS; METHYLATION; MICE; PLURIPOTENT STEM CELLS; SUCCINIC ACID; TRANSCRIPTION, GENETIC;

EID: 84925503908     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/nature13981     Document Type: Article

References (30)

1. Lunt, S. Y. & Vander Heiden, M. G. Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu. Rev. Cell Dev. Biol. 27, 441-464 (2011).
2. Eagle, H., Oyama, V. I., Levy, M., Horton, C. L. & Fleischman, R. The growth response of mammalian cells in tissue culture to L-glutamine and L-glutamic acid. J. Biol. Chem. 218, 607-616 (1956).
3. Ying, Q. L. et al. The ground state of embryonic stem cell self-renewal. Nature 453, 519-523 (2008).
4. Nichols, J., Silva, J., Roode, M. & Smith, A. Suppression of Erk signalling promotes ground state pluripotency in the mouse embryo. Development 136, 3215-3222 (2009).
5. Smith, Z. D. et al. A unique regulatory phase of DNA methylation in the early mammalian embryo. Nature 484, 339-344 (2012).
6. Wray, J., Kalkan, T. & Smith, A. G. The ground state of pluripotency. Biochem. Soc. Trans. 38, 1027-1032 (2010).
7. Leitch, H. G. et al. Naive pluripotency is associated with global DNA hypomethylation. Nature Struct. Mol. Biol. 20, 311-316 (2013).
8. Ficz, G. et al. FGF signaling inhibition in ESCs drives rapid genome-wide demethylation to the epigenetic ground state of pluripotency. Cell Stem Cell 13, 351-359 (2013).
9. Habibi, E. et al.Whole-genomebisulfite sequencing of two distinct interconvertible DNA methylomes of mouse embryonic stem cells. Cell Stem Cell 13, 360-369 (2013).
10. Borgel, J. et al. Targets and dynamics of promoter DNA methylation during early mouse development. Nature Genet. 42, 1093-1100 (2010).
11. Marks, H. et al. The transcriptional and epigenomic foundations of ground state pluripotency. Cell 149, 590-604 (2012).
12. Ying, Q. L., Nichols, J., Chambers, I. & Smith, A. BMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3. Cell 115, 281-292 (2003).
13. Zhang, J., Nuebel, E., Daley, G. Q., Koehler, C. M.& Teitell, M. A.Metabolic regulation in pluripotent stem cells during reprogramming and self-renewal. Cell Stem Cell 11, 589-595 (2012).
14. Kaelin, W. G. Jr. Cancer and altered metabolism: potential importance of hypoxiainducible factor and 2-oxoglutarate-dependent dioxygenases. Cold Spring Harb. Symp. Quant. Biol. 76, 335-345 (2011).
15. Cloos, P. A., Christensen, J., Agger, K. & Helin, K. Erasing the methyl mark: histone demethylases at the center of cellular differentiation and disease. Genes Dev. 22, 1115-1140 (2008).
16. Kruidenier, L. et al. A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature 488, 404-408 (2012).
17. Bernstein, B. E. et al. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125, 315-326 (2006).
18. Boyer, L. A. et al. Polycombcomplexes repress developmental regulators inmurine embryonic stem cells. Nature 441, 349-353 (2006).
19. Mikkelsen, T. S. et al. Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448, 553-560 (2007).
20. Blaschke, K. et al. Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. Nature 500, 222-226 (2013).
21. Hackett, J. A. et al. Synergistic mechanisms of DNA demethylation during transition to ground-state pluripotency. Stem Cell Reports 1, 518-531 (2013).
22. Faddah, D. A. et al. Single-cell analysis reveals that expression of Nanog is biallelic and equally variable as that of other pluripotency factors inmouse ESCs. Cell Stem Cell 13, 23-29 (2013).
23. Shipony, Z. et al. Dynamic and static maintenance of epigenetic memory in pluripotent and somatic cells. Nature 513, 115-119 (2014).
24. Markoulaki, S., Meissner, A. & Jaenisch, R. Somatic cell nuclear transfer and derivation of embryonic stemcells in the mouse. Methods 45, 101-114 (2008).
25. Dawlaty, M. M. et al. Combined deficiency of Tet1 and Tet2 causes epigenetic abnormalities but is compatible with postnatal development. Dev. Cell 24, 310-323 (2013).
26. Buganim, Y. et al. Single-cell expression analyses during cellular reprogramming reveal an early stochastic and a late hierarchic phase. Cell 150, 1209-1222 (2012).
27. Millard, P., Letisse, F., Sokol, S. & Portais, J. C. IsoCor: correcting MS data in isotope labeling experiments. Bioinformatics 28, 1294-1296 (2012).
28. Yuan, J., Bennett, B. D. & Rabinowitz, J. D. Kinetic flux profiling for quantitation of cellular metabolic fluxes. Nature Protocols 3, 1328-1340 (2008).
29. Bligh, E. G. & Dyer, W. J. A rapid method of total lipid extraction and purification. Can. J. Biochem. Physiol. 37, 911-917 (1959).
30. Ran, F. A. et al. Genome engineering using the CRISPR-Cas9 system. Nature Protocols 8, 2281-2308 (2013).