NRF2 Orchestrates the Metabolic Shift during Induced Pluripotent Stem Cell Reprogramming

Cell Reports

Volumn 14, Issue 8, 2016, Pages 1883-1891

  Hawkins, Kate E ^a   Joy, Shona ^a,b   Delhove, Juliette M K M ^a,b,c   Kotiadis, Vassilios N ^b   Fernandez, Emilio ^d,e   Fitzpatrick, Lorna M ^a,g   Whiteford, James R ^f   King, Peter J ^f   Bolanos, Juan P ^d,e   Duchen, Michael R ^b   Waddington, Simon N ^b,c   McKay, Tristan R ^a,g  

^a ST GEORGE'S UNIVERSITY OF LONDON   (United Kingdom)

^b UNIVERSITY COLLEGE LONDON   (United Kingdom)

^c UNIVERSITY OF THE WITWATERSRAND   (South Africa)

^d UNIVERSITY OF SALAMANCA   (Spain)

^e HOSPITAL UNIVERSITARIO DE SALAMANCA   (Spain)

^f QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

^g MANCHESTER METROPOLITAN UNIVERSITY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

HEME OXYGENASE 1; HYPOXIA INDUCIBLE FACTOR 1ALPHA; HYPOXIA INDUCIBLE FACTOR 2ALPHA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; KELCH LIKE ECH ASSOCIATED PROTEIN 1; NOTCH RECEPTOR; TRANSCRIPTION FACTOR AP 1; TRANSCRIPTION FACTOR NFAT; TRANSCRIPTION FACTOR NRF2; HIF1A PROTEIN, HUMAN; KEAP1 PROTEIN, HUMAN; LUCIFERASE; NFE2L2 PROTEIN, HUMAN; REACTIVE OXYGEN METABOLITE;

ARTICLE; AUTOPHAGY; CELL NUCLEUS; CELL PROLIFERATION; CONTROLLED STUDY; CYTOPLASM; FIBROBLAST; GLYCOLYSIS; HUMAN; HUMAN CELL; NUCLEAR REPROGRAMMING; OXIDATIVE PHOSPHORYLATION; OXYGEN CONSUMPTION; PLURIPOTENT STEM CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN TARGETING; UPREGULATION; CHEMISTRY; CYTOLOGY; DERMIS; GENE EXPRESSION REGULATION; GENE VECTOR; GENETIC TRANSDUCTION; GENETICS; INDUCED PLURIPOTENT STEM CELL; LENTIVIRINAE; METABOLISM; PENTOSE PHOSPHATE CYCLE; REPORTER GENE; SIGNAL TRANSDUCTION;

CELLULAR REPROGRAMMING; DERMIS; FIBROBLASTS; GENE EXPRESSION REGULATION; GENES, REPORTER; GENETIC VECTORS; GLYCOLYSIS; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; INDUCED PLURIPOTENT STEM CELLS; KELCH-LIKE ECH-ASSOCIATED PROTEIN 1; LENTIVIRUS; LUCIFERASES; NF-E2-RELATED FACTOR 2; NF-KAPPA B; OXIDATIVE PHOSPHORYLATION; PENTOSE PHOSPHATE PATHWAY; REACTIVE OXYGEN SPECIES; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTOR AP-1; TRANSDUCTION, GENETIC;

EID: 84959240661     PISSN: None     EISSN: 22111247     Source Type: Journal    
DOI: 10.1016/j.celrep.2016.02.003     Document Type: Article

References (52)

1. Baird L., Llères D., Swift S., Dinkova-Kostova A.T. Regulatory flexibility in the Nrf2-mediated stress response is conferred by conformational cycling of the Keap1-Nrf2 protein complex. Proc. Natl. Acad. Sci. USA 2013, 110:15259-15264.
2. Buckley S.M.K., Delhove J.M.K.M., Perocheau D.P., Karda R., Rahim A.A., Howe S.J., Ward N.J., Birrell M.A., Belvisi M.G., Arbuthnot P., et al. In vivo bioimaging with tissue-specific transcription factor activated luciferase reporters. Sci. Rep. 2015, 5:11842.
3. Chen H.-F., Kuo H.-C., Lin S.-P., Chien C.-L., Chiang M.-S., Ho H.-N. Hypoxic culture maintains self-renewal and enhances embryoid body formation of human embryonic stem cells. Tissue Eng. Part A 2010, 16:2901-2913.
4. Cho Y.M., Kwon S., Pak Y.K., Seol H.W., Choi Y.M., Park J., Park K.S., Lee H.K. Dynamic changes in mitochondrial biogenesis and antioxidant enzymes during the spontaneous differentiation of human embryonic stem cells. Biochem. Biophys. Res. Commun. 2006, 348:1472-1478.
5. Chowdhry S., Zhang Y., McMahon M., Sutherland C., Cuadrado A., Hayes J.D. Nrf2 is controlled by two distinct β-TrCP recognition motifs in its Neh6 domain, one of which can be modulated by GSK-3 activity. Oncogene 2013, 32:3765-3781.
6. Danet G.H., Pan Y., Luongo J.L., Bonnet D.A., Simon M.C. Expansion of human SCID-repopulating cells under hypoxic conditions. J. Clin. Invest. 2003, 112:126-135.
7. Esteban M.A., Wang T., Qin B., Yang J., Qin D., Cai J., Li W., Weng Z., Chen J., Ni S., et al. Vitamin C enhances the generation of mouse and human induced pluripotent stem cells. Cell Stem Cell 2010, 6:71-79.
8. Ezashi T., Das P., Roberts R.M. Low O2 tensions and the prevention of differentiation of hES cells. Proc. Natl. Acad. Sci. USA 2005, 102:4783-4788.
9. Finley L.W.S., Carracedo A., Lee J., Souza A., Egia A., Zhang J., Teruya-Feldstein J., Moreira P.I., Cardoso S.M., Clish C.B., et al. SIRT3 opposes reprogramming of cancer cell metabolism through HIF1α destabilization. Cancer Cell 2011, 19:416-428.
10. Folmes C.D.L., Nelson T.J., Martinez-Fernandez A., Arrell D.K., Lindor J.Z., Dzeja P.P., Ikeda Y., Perez-Terzic C., Terzic A. Somatic oxidative bioenergetics transitions into pluripotency-dependent glycolysis to facilitate nuclear reprogramming. Cell Metab. 2011, 14:264-271.
11. Golipour A., David L., Liu Y., Jayakumaran G., Hirsch C.L., Trcka D., Wrana J.L. A late transition in somatic cell reprogramming requires regulators distinct from the pluripotency network. Cell Stem Cell 2012, 11:769-782.
12. Gonchar O., Mankovska I. Antioxidant System in Adaptation to Intermittent Hypoxia. J. Biol. Sci. 2010, 10:545-554.
13. Hanna J., Saha K., Pando B., van Zon J., Lengner C.J., Creyghton M.P., van Oudenaarden A., Jaenisch R. Direct cell reprogramming is a stochastic process amenable to acceleration. Nature 2009, 462:595-601.
14. Hansson J., Rafiee M.R., Reiland S., Polo J.M., Gehring J., Okawa S., Huber W., Hochedlinger K., Krijgsveld J. Highly coordinated proteome dynamics during reprogramming of somatic cells to pluripotency. Cell Rep. 2012, 2:1579-1592.
15. Hayashi K., Dan K., Goto F., Tshuchihashi N., Nomura Y., Fujioka M., Kanzaki S., Ogawa K. The autophagy pathway maintained signaling crosstalk with the Keap1-Nrf2 system through p62 in auditory cells under oxidative stress. Cell. Signal. 2015, 27:382-393.
16. Herrero-Mendez A., Almeida A., Fernández E., Maestre C., Moncada S., Bolaños J.P. The bioenergetic and antioxidant status of neurons is controlled by continuous degradation of a key glycolytic enzyme by APC/C-Cdh1. Nat. Cell Biol. 2009, 11:747-752.
17. Ichida J.K., Tcw J., Williams L.A., Carter A.C., Shi Y., Moura M.T., Ziller M., Singh S., Amabile G., Bock C., et al. Notch inhibition allows oncogene-independent generation of iPS cells. Nat. Chem. Biol. 2014, 10:632-639.
18. Ichimura Y., Waguri S., Sou Y.-S., Kageyama S., Hasegawa J., Ishimura R., Saito T., Yang Y., Kouno T., Fukutomi T., et al. Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective autophagy. Mol. Cell 2013, 51:618-631.
19. Jacobson J., Duchen M.R., Hothersall J., Clark J.B., Heales S.J.R. Induction of mitochondrial oxidative stress in astrocytes by nitric oxide precedes disruption of energy metabolism. J. Neurochem. 2005, 95:388-395.
20. Jang J., Wang Y., Kim H.-S., Lalli M.A., Kosik K.S. Nrf2, a regulator of the proteasome, controls self-renewal and pluripotency in human embryonic stem cells. Stem Cells 2014, 32:2616-2625.
21. Ji J., Sharma V., Qi S., Guarch M.E., Zhao P., Luo Z., Fan W., Wang Y., Mbabaali F., Neculai D., et al. Antioxidant supplementation reduces genomic aberrations in human induced pluripotent stem cells. Stem Cell Reports 2014, 2:44-51.
22. Larrabee M.G. Evaluation of the pentose phosphate pathway from 14CO2 data. Fallibility of a classic equation when applied to non-homogeneous tissues. Biochem. J. 1990, 272:127-132.
23. Liu W., Long Q., Chen K., Li S., Xiang G., Chen S., Liu X., Li Y., Yang L., Dong D., et al. Mitochondrial metabolism transition cooperates with nuclear reprogramming during induced pluripotent stem cell generation. Biochem. Biophys. Res. Commun. 2013, 431:767-771.
24. Lonergan T., Brenner C., Bavister B. Differentiation-related changes in mitochondrial properties as indicators of stem cell competence. J. Cell. Physiol. 2006, 208:149-153.
25. Mah N., Wang Y., Liao M.-C., Prigione A., Jozefczuk J., Lichtner B., Wolfrum K., Haltmeier M., Flöttmann M., Schaefer M., et al. Molecular insights into reprogramming-initiation events mediated by the OSKM gene regulatory network. PLoS ONE 2011, 6:e24351.
26. Malec V., Gottschald O.R., Li S., Rose F., Seeger W., Hänze J. HIF-1 alpha signaling is augmented during intermittent hypoxia by induction of the Nrf2 pathway in NOX1-expressing adenocarcinoma A549 cells. Free Radic. Biol. Med. 2010, 48:1626-1635.
27. Manganelli G., Fico A., Masullo U., Pizzolongo F., Cimmino A., Filosa S. Modulation of the pentose phosphate pathway induces endodermal differentiation in embryonic stem cells. PLoS ONE 2012, 7:e29321.
28. Mathieu J., Zhou W., Xing Y., Sperber H., Ferreccio A., Agoston Z., Kuppusamy K.T., Moon R.T., Ruohola-Baker H. Hypoxia-inducible factors have distinct and stage-specific roles during reprogramming of human cells to pluripotency. Cell Stem Cell 2014, 14:592-605.
29. McMahon M., Thomas N., Itoh K., Yamamoto M., Hayes J.D. Dimerization of substrate adaptors can facilitate cullin-mediated ubiquitylation of proteins by a "tethering" mechanism: a two-site interaction model for the Nrf2-Keap1 complex. J. Biol. Chem. 2006, 281:24756-24768.
30. Mitsuishi Y., Taguchi K., Kawatani Y., Shibata T., Nukiwa T., Aburatani H., Yamamoto M., Motohashi H. Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming. Cancer Cell 2012, 22:66-79.
31. Morrison S.J., Csete M., Groves A.K., Melega W., Wold B., Anderson D.J. Culture in reduced levels of oxygen promotes clonogenic sympathoadrenal differentiation by isolated neural crest stem cells. J. Neurosci. 2000, 20:7370-7376.
32. O'Malley J., Skylaki S., Iwabuchi K.A., Chantzoura E., Ruetz T., Johnsson A., Tomlinson S.R., Linnarsson S., Kaji K. High-resolution analysis with novel cell-surface markers identifies routes to iPS cells. Nature 2013, 499:88-91.
33. Palomäki S., Pietilä M., Laitinen S., Pesälä J., Sormunen R., Lehenkari P., Koivunen P. HIF-1α is upregulated in human mesenchymal stem cells. Stem Cells 2013, 31:1902-1909.
34. Panopoulos A.D., Yanes O., Ruiz S., Kida Y.S., Diep D., Tautenhahn R., Herrerías A., Batchelder E.M., Plongthongkum N., Lutz M., et al. The metabolome of induced pluripotent stem cells reveals metabolic changes occurring in somatic cell reprogramming. Cell Res. 2012, 22:168-177.
35. Park K.-K., Jung E., Chon S.-K., Seo M., Kim H.W., Park T. Finding of TRE (TPA responsive element) in the sequence of human taurine transporter promoter. Adv. Exp. Med. Biol. 2003, 526:159-166.
36. Park S.-J., Yeo H.C., Kang N.-Y., Kim H., Lin J., Ha H.-H., Vendrell M., Lee J.-S., Chandran Y., Lee D.-Y., et al. Mechanistic elements and critical factors of cellular reprogramming revealed by stepwise global gene expression analyses. Stem Cell Res. (Amst.) 2014, 12:730-741.
37. Polo J.M., Anderssen E., Walsh R.M., Schwarz B.A., Nefzger C.M., Lim S.M., Borkent M., Apostolou E., Alaei S., Cloutier J., et al. A molecular roadmap of reprogramming somatic cells into iPS cells. Cell 2012, 151:1617-1632.
38. 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 2010, 28:721-733.
39. Prigione A., Rohwer N., Hoffmann S., Mlody B., Drews K., Bukowiecki R., Blümlein K., Wanker E.E., Ralser M., Cramer T., Adjaye J. HIF1α modulates cell fate reprogramming through early glycolytic shift and upregulation of PDK1-3 and PKM2. Stem Cells 2014, 32:364-376.
40. Reuter S., Gupta S.C., Chaturvedi M.M., Aggarwal B.B. Oxidative stress, inflammation, and cancer: how are they linked?. Free Radic. Biol. Med. 2010, 49:1603-1616.
41. Samavarchi-Tehrani P., Golipour A., David L., Sung H.K., Beyer T.A., Datti A., Woltjen K., Nagy A., Wrana J.L. Functional genomics reveals a BMP-driven mesenchymal-to-epithelial transition in the initiation of somatic cell reprogramming. Cell Stem Cell 2010, 7:64-77.
42. Shimada H., Hashimoto Y., Nakada A., Shigeno K., Nakamura T. Accelerated generation of human induced pluripotent stem cells with retroviral transduction and chemical inhibitors under physiological hypoxia. Biochem. Biophys. Res. Commun. 2012, 417:659-664.
43. Singh A., Happel C., Manna S.K., Acquaah-Mensah G., Carrerero J., Kumar S., Nasipuri P., Krausz K.W., Wakabayashi N., Dewi R., et al. Transcription factor NRF2 regulates miR-1 and miR-206 to drive tumorigenesis. J. Clin. Invest. 2013, 123:2921-2934.
44. Studer L., Csete M., Lee S.H., Kabbani N., Walikonis J., Wold B., McKay R. Enhanced proliferation, survival, and dopaminergic differentiation of CNS precursors in lowered oxygen. J. Neurosci. 2000, 20:7377-7383.
45. Takahashi K., Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006, 126:663-676.
46. Tsai J.J., Dudakov J.A., Takahashi K., Shieh J.-H., Velardi E., Holland A.M., Singer N.V., West M.L., Smith O.M., Young L.F., et al. Nrf2 regulates haematopoietic stem cell function. Nat. Cell Biol. 2013, 15:309-316.
47. Varum S., Rodrigues A.S., Moura M.B., Momcilovic O., Easley C.A., Ramalho-Santos J., Van Houten B., Schatten G. Energy metabolism in human pluripotent stem cells and their differentiated counterparts. PLoS ONE 2011, 6:e20914.
48. Yoshida Y., Takahashi K., Okita K., Ichisaka T., Yamanaka S. Hypoxia enhances the generation of induced pluripotent stem cells. Cell Stem Cell 2009, 5:237-241.
49. Yu J., Hu K., Smuga-Otto K., Tian S., Stewart R., Slukvin I.I., Thomson J.A. Human induced pluripotent stem cells free of vector and transgene sequences. Science 2009, 324:797-801.
50. Zhang J., Khvorostov I., Hong J.S., Oktay Y., Vergnes L., Nuebel E., Wahjudi P.N., Setoguchi K., Wang G., Do A., et al. UCP2 regulates energy metabolism and differentiation potential of human pluripotent stem cells. EMBO J. 2011, 30:4860-4873.
51. Zhang X., Yalcin S., Lee D.-F., Yeh T.-Y.J., Lee S.-M., Su J., Mungamuri S.K., Rimmelé P., Kennedy M., Sellers R., et al. FOXO1 is an essential regulator of pluripotency in human embryonic stem cells. Nat. Cell Biol. 2011, 13:1092-1099.
52. Zhu L., Zhang S., Jin Y. Foxd3 suppresses NFAT-mediated differentiation to maintain self-renewal of embryonic stem cells. EMBO Rep. 2014, 15:1286-1296.