Induced Pluripotency and Oncogenic Transformation Are Related Processes
Publication: Stem Cells and Development
Volume 22, Issue Number 1
Abstract
Induced pluripotent stem cells (iPSCs) have the potential for creating patient-specific regenerative medicine therapies, but the links between pluripotency and tumorigenicity raise important safety concerns. More specifically, the methods employed for the production of iPSCs and oncogenic foci (OF), a form of in vitro produced tumor cells, are surprisingly similar, raising potential concerns about iPSCs. To test the hypotheses that iPSCs and OF are related cell types and, more broadly, that the induction of pluripotency and tumorigenicity are related processes, we produced iPSCs and OF in parallel from common parental fibroblasts. When we compared the transcriptomes of these iPSCs and OF to their parental fibroblasts, similar transcriptional changes were observed in both iPSCs and OF. A significant number of genes repressed during the iPSC formation were also repressed in OF, including a large cohort of differentiation-associated genes. iPSCs and OF shared a limited number of genes that were upregulated relative to parental fibroblasts, but gene ontology analysis pointed toward monosaccharide metabolism as upregulated in both iPSCs and OF. iPSCs and OF were distinct in that only iPSCs activated a host of pluripotency-related genes, while OF activated cellular damage and specific metabolic pathways. We reprogrammed oncogenic foci (ROF) to produce iPSC-like cells, a process dependent on Nanog. However, the ROF had reduced differentiation potential compared to iPSC, suggesting that oncogenic transformation leads to cellular changes that impair complete reprogramming. Taken together, these findings support a model in which OF and iPSCs are related, yet distinct cell types, and in which induced pluripotency and induced tumorigenesis are similar processes.
Get full access to this article
View all available purchase options and get full access to this article.
References
1.
Okita KT IchisakaS Yamanaka2007. Generation of germline-competent induced pluripotent stem cellsNature448313-317. 1. Okita K, T Ichisaka and S Yamanaka. (2007). Generation of germline-competent induced pluripotent stem cells. Nature 448:313–317.
2.
Takahashi KS Yamanaka2006. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factorsCell126663-676. 2. Takahashi K and S Yamanaka. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676.
3.
Wernig MA MeissnerR ForemanT BrambrinkM KuK HochedlingerBE BernsteinR Jaenisch2007. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like stateNature448260-262. 3. Wernig M, A Meissner, R Foreman, T Brambrink, M Ku, K Hochedlinger, BE Bernstein and R Jaenisch. (2007). In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 448:260–262.
4.
Yamanaka SK Takahashi2006. [Induction of pluripotent stem cells from mouse fibroblast cultures]Tanpakushitsu Kakusan Koso512346-2351. 4. Yamanaka S and K Takahashi. (2006). [Induction of pluripotent stem cells from mouse fibroblast cultures]. Tanpakushitsu Kakusan Koso 51:2346–2351.
5.
Park IHR ZhaoJA WestA YabuuchiH HuoTA IncePH LerouMW LenschGQ Daley2008. Reprogramming of human somatic cells to pluripotency with defined factorsNature451141-146. 5. Park IH, R Zhao, JA West, A Yabuuchi, H Huo, TA Ince, PH Lerou, MW Lensch and GQ Daley. (2008). Reprogramming of human somatic cells to pluripotency with defined factors. Nature 451:141–146.
6.
Nakagawa MM KoyanagiK TanabeK TakahashiT IchisakaT AoiY MochidukiN TakizawaS Yamanaka2008. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblastsNat Biotechnol26101-106. 6. Nakagawa M, M Koyanagi, K Tanabe, K Takahashi, T Ichisaka, T Aoi, Y Mochiduki, N Takizawa and S Yamanaka. (2008). Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol 26:101–106.
7.
Chin MHMJ MasonW XieS VoliniaM SingerC PetersonG AmbartsumyanO AimiuwuL Richter et al.2009. Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signaturesCell Stem Cell5111-123. 7. Chin MH, MJ Mason, W Xie, S Volinia, M Singer, C Peterson, G Ambartsumyan, O Aimiuwu, L Richter, et al. (2009). Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures. Cell Stem Cell 5:111–123.
8.
Chiou SHCC YuCY HuangSC LinCJ LiuTH TsaiSH ChouCS ChienHH KuJF Lo2008. Positive correlations of Oct-4 and Nanog in oral cancer stem-like cells and high-grade oral squamous cell carcinomaClin Cancer Res144085-4095. 8. Chiou SH, CC Yu, CY Huang, SC Lin, CJ Liu, TH Tsai, SH Chou, CS Chien, HH Ku and JF Lo. (2008). Positive correlations of Oct-4 and Nanog in oral cancer stem-like cells and high-grade oral squamous cell carcinoma. Clin Cancer Res 14:4085–4095.
9.
Liu AL ChengJ DuY PengRW AllanL WeiJ LiD Cao2010. Diagnostic utility of novel stem cell markers SALL4, OCT4, NANOG, SOX2, UTF1, and TCL1 in primary mediastinal germ cell tumorsAm J Surg Pathol34697-706. 9. Liu A, L Cheng, J Du, Y Peng, RW Allan, L Wei, J Li and D Cao. (2010). Diagnostic utility of novel stem cell markers SALL4, OCT4, NANOG, SOX2, UTF1, and TCL1 in primary mediastinal germ cell tumors. Am J Surg Pathol 34:697–706.
10.
Meng HMP ZhengXY WangC LiuHM SuiSJ WuJ ZhouYQ DingJM Li2010. Overexpression of nanog predicts tumor progression and poor prognosis in colorectal cancerCancer Biol Ther9295-302. 10. Meng HM, P Zheng, XY Wang, C Liu, HM Sui, SJ Wu, J Zhou, YQ Ding and JM Li. (2010). Overexpression of nanog predicts tumor progression and poor prognosis in colorectal cancer. Cancer Biol Ther 9: 295–302.
11.
Knoepfler PS2009. Deconstructing stem cell tumorigenicity: a roadmap to safe regenerative medicineStem Cells271050-1056. 11. Knoepfler PS. (2009). Deconstructing stem cell tumorigenicity: a roadmap to safe regenerative medicine. Stem Cells 27:1050–1056.
12.
Miura KY OkadaT AoiA OkadaK TakahashiK OkitaM NakagawaM KoyanagiK Tanabe et al.2009. Variation in the safety of induced pluripotent stem cell linesNat Biotechnol27743-745. 12. Miura K, Y Okada, T Aoi, A Okada, K Takahashi, K Okita, M Nakagawa, M Koyanagi, K Tanabe, et al. (2009). Variation in the safety of induced pluripotent stem cell lines. Nat Biotechnol 27:743–745.
13.
Blum BN Benvenisty2008. The tumorigenicity of human embryonic stem cellsAdv Cancer Res100133-158. 13. Blum B and N Benvenisty. (2008). The tumorigenicity of human embryonic stem cells. Adv Cancer Res 100:133–158.
14.
Wong DJH LiuTW RidkyD CassarinoE SegalHY Chang2008. Module map of stem cell genes guides creation of epithelial cancer stem cellsCell Stem Cell2333-344. 14. Wong DJ, H Liu, TW Ridky, D Cassarino, E Segal and HY Chang. (2008). Module map of stem cell genes guides creation of epithelial cancer stem cells. Cell Stem Cell 2:333–344.
15.
Ben-Porath IMW ThomsonVJ CareyR GeGW BellA RegevRA Weinberg2008. An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumorsNat Genet40499-507. 15. Ben-Porath I, MW Thomson, VJ Carey, R Ge, GW Bell, A Regev and RA Weinberg. (2008). An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet 40:499–507.
16.
Varlakhanova NVRF CottermanWN de VriesJ MorganLR DonahueS MurrayBB KnowlesPS Knoepfler2010. myc maintains embryonic stem cell pluripotency and self-renewalDifferentiation809-19. 16. Varlakhanova NV, RF Cotterman, WN de Vries, J Morgan, LR Donahue, S Murray, BB Knowles and PS Knoepfler. (2010). myc maintains embryonic stem cell pluripotency and self-renewal. Differentiation 80:9–19.
17.
Lin CHC LinH TanakaML FeroRN Eisenman2009. Gene regulation and epigenetic remodeling in murine embryonic stem cells by c-MycPLoS One4e7839. 17. Lin CH, C Lin, H Tanaka, ML Fero and RN Eisenman. (2009). Gene regulation and epigenetic remodeling in murine embryonic stem cells by c-Myc. PLoS One 4:e7839.
18.
Lin CHAL JacksonJ GuoPS LinsleyRN Eisenman2009. Myc-regulated microRNAs attenuate embryonic stem cell differentiationEMBO J283157-3170. 18. Lin CH, AL Jackson, J Guo, PS Linsley and RN Eisenman. (2009). Myc-regulated microRNAs attenuate embryonic stem cell differentiation. EMBO J 28:3157–3170.
19.
Varlakhanova NR CottermanK BradnamI KorfPS Knoepfler2011. Myc and Miz-1 have coordinate genomic functions including targeting Hox genes in human embryonic stem cellsEpigenetics Chromatin420. 19. Varlakhanova N, R Cotterman, K Bradnam, I Korf and PS Knoepfler. (2011). Myc and Miz-1 have coordinate genomic functions including targeting Hox genes in human embryonic stem cells. Epigenetics Chromatin 4:20.
20.
Sridharan RJ TchieuMJ MasonR YachechkoE KuoyS HorvathQ ZhouK Plath2009. Role of the murine reprogramming factors in the induction of pluripotencyCell136364-377. 20. Sridharan R, J Tchieu, MJ Mason, R Yachechko, E Kuoy, S Horvath, Q Zhou and K Plath. (2009). Role of the murine reprogramming factors in the induction of pluripotency. Cell 136:364–377.
21.
Cotterman RPS Knoepfler2009. N-Myc regulates expression of pluripotency genes in neuroblastoma including lif, klf2, klf4, and lin28bPLoS One4e5799. 21. Cotterman R and PS Knoepfler. (2009). N-Myc regulates expression of pluripotency genes in neuroblastoma including lif, klf2, klf4, and lin28b. PLoS One 4:e5799.
22.
Devine MJM RytenP VodickaAJ ThomsonT BurdonH HouldenF CavaleriM NaganoNJ Drummond et al.2011. Parkinson's disease induced pluripotent stem cells with triplication of the alpha-synuclein locusNat Commun2440. 22. Devine MJ, M Ryten, P Vodicka, AJ Thomson, T Burdon, H Houlden, F Cavaleri, M Nagano, NJ Drummond, et al. (2011). Parkinson's disease induced pluripotent stem cells with triplication of the alpha-synuclein locus. Nat Commun 2:440.
23.
Yancopoulos GDPD NisenA TesfayeNE KohlMP GoldfarbFW Alt1985. N-myc can cooperate with ras to transform normal cells in cultureProc Natl Acad Sci U S A825455-5459. 23. Yancopoulos GD, PD Nisen, A Tesfaye, NE Kohl, MP Goldfarb and FW Alt. (1985). N-myc can cooperate with ras to transform normal cells in culture. Proc Natl Acad Sci U S A 82:5455–5459.
24.
Keath EJPG CaimiMD Cole1984. Fiboblast lines expressing activated c-myc oncogenes are tumorigenic in nude mice and syngeneic animalsCell39339-348. 24. Keath EJ, PG Caimi and MD Cole. (1984). Fiboblast lines expressing activated c-myc oncogenes are tumorigenic in nude mice and syngeneic animals. Cell 39:339–348.
25.
Breitman MLR VignePK Vogt1980. Growth-related alterations induced in chick embryo fibroblasts by src-gene deletion mutants of the Schmidt-Ruppin strain of Rous sarcoma virusCold Spring Harb Symp Quant Biol44Pt 21047-1055. 25. Breitman ML, R Vigne and PK Vogt. (1980). Growth-related alterations induced in chick embryo fibroblasts by src-gene deletion mutants of the Schmidt-Ruppin strain of Rous sarcoma virus. Cold Spring Harb Symp Quant Biol 44 Pt 2:1047–1055.
26.
Yu JMA VodyanikK Smuga-OttoJ Antosiewicz-BourgetJL FraneS TianJ NieGA JonsdottirV Ruotti et al.2007. Induced pluripotent stem cell lines derived from human somatic cellsScience3181917-1920. 26. Yu J, MA Vodyanik, K Smuga-Otto, J Antosiewicz-Bourget, JL Frane, S Tian, J Nie, GA Jonsdottir, V Ruotti, et al. (2007). Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920.
27.
Aoi TK YaeM NakagawaT IchisakaK OkitaK TakahashiT ChibaS Yamanaka2008. Generation of pluripotent stem cells from adult mouse liver and stomach cellsScience321699-702. 27. Aoi T, K Yae, M Nakagawa, T Ichisaka, K Okita, K Takahashi, T Chiba and S Yamanaka. (2008). Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science 321:699–702.
28.
Zhao YX YinH QinF ZhuH LiuW YangQ ZhangC XiangP Hou et al.2008. Two supporting factors greatly improve the efficiency of human iPSC generationCell Stem Cell3475-479. 28. Zhao Y, X Yin, H Qin, F Zhu, H Liu, W Yang, Q Zhang, C Xiang, P Hou, et al. (2008). Two supporting factors greatly improve the efficiency of human iPSC generation. Cell Stem Cell 3:475–479.
29.
Hong HK TakahashiT IchisakaT AoiO KanagawaM NakagawaK OkitaS Yamanaka2009. Suppression of induced pluripotent stem cell generation by the p53-p21 pathwayNature4601132-1135. 29. Hong H, K Takahashi, T Ichisaka, T Aoi, O Kanagawa, M Nakagawa, K Okita and S Yamanaka. (2009). Suppression of induced pluripotent stem cell generation by the p53-p21 pathway. Nature 460:1132–1135.
30.
Kawamura TJ SuzukiYV WangS MenendezLB MoreraA RayaGM WahlJC Belmonte2009. Linking the p53 tumour suppressor pathway to somatic cell reprogrammingNature4601140-1144. 30. Kawamura T, J Suzuki, YV Wang, S Menendez, LB Morera, A Raya, GM Wahl and JC Belmonte. (2009). Linking the p53 tumour suppressor pathway to somatic cell reprogramming. Nature 460:1140–1144.
31.
Marion RMK StratiH LiM MurgaR BlancoS OrtegaO Fernandez-CapetilloM SerranoMA Blasco2009. A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrityNature4601149-1153. 31. Marion RM, K Strati, H Li, M Murga, R Blanco, S Ortega, O Fernandez-Capetillo, M Serrano and MA Blasco. (2009). A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity. Nature 460:1149–1153.
32.
Utikal JJM PoloM StadtfeldN MaheraliW KulalertRM WalshA KhalilJG RheinwaldK Hochedlinger2009. Immortalization eliminates a roadblock during cellular reprogramming into iPS cellsNature4601145-1148. 32. Utikal J, JM Polo, M Stadtfeld, N Maherali, W Kulalert, RM Walsh, A Khalil, JG Rheinwald and K Hochedlinger. (2009). Immortalization eliminates a roadblock during cellular reprogramming into iPS cells. Nature 460:1145–1148.
33.
Li HM ColladoA VillasanteK StratiS OrtegaM CanameroMA BlascoM Serrano2009. The Ink4/Arf locus is a barrier for iPS cell reprogrammingNature4601136-1139. 33. Li H, M Collado, A Villasante, K Strati, S Ortega, M Canamero, MA Blasco and M Serrano. (2009). The Ink4/Arf locus is a barrier for iPS cell reprogramming. Nature 460:1136–1139.
34.
Hinds PC FinlayAJ Levine1989. Mutation is required to activate the p53 gene for cooperation with the ras oncogene and transformationJ Virol63739-746. 34. Hinds P, C Finlay and AJ Levine. (1989). Mutation is required to activate the p53 gene for cooperation with the ras oncogene and transformation. J Virol 63:739–746.
35.
Rohaly GK KorfS DehdeI Dornreiter2010. Simian virus 40 activates ATR-Delta p53 signaling to override cell cycle and DNA replication controlJ Virol8410727-10747. 35. Rohaly G, K Korf, S Dehde and I Dornreiter. (2010). Simian virus 40 activates ATR-Delta p53 signaling to override cell cycle and DNA replication control. J Virol 84:10727–10747.
36.
Chou BKP MaliX HuangZ YeSN DoweyLM ResarC ZouYA ZhangJ TongL Cheng2011. Efficient human iPS cell derivation by a non-integrating plasmid from blood cells with unique epigenetic and gene expression signaturesCell Res21518-529. 36. Chou BK, P Mali, X Huang, Z Ye, SN Dowey, LM Resar, C Zou, YA Zhang, J Tong and L Cheng. (2011). Efficient human iPS cell derivation by a non-integrating plasmid from blood cells with unique epigenetic and gene expression signatures. Cell Res 21:518–529.
37.
Feng BJ JiangP KrausJH NgJC HengYS ChanLP YawW ZhangYH Loh et al.2009. Reprogramming of fibroblasts into induced pluripotent stem cells with orphan nuclear receptor EsrrbNat Cell Biol11197-203. 37. Feng B, J Jiang, P Kraus, JH Ng, JC Heng, YS Chan, LP Yaw, W Zhang, YH Loh, et al. (2009). Reprogramming of fibroblasts into induced pluripotent stem cells with orphan nuclear receptor Esrrb. Nat Cell Biol 11:197–203.
38.
Kunisato AM WakatsukiY KodamaH ShinbaI IshidaK Nagao2010. Generation of induced pluripotent stem cells by efficient reprogramming of adult bone marrow cellsStem Cells Dev19229-238. 38. Kunisato A, M Wakatsuki, Y Kodama, H Shinba, I Ishida and K Nagao. (2010). Generation of induced pluripotent stem cells by efficient reprogramming of adult bone marrow cells. Stem Cells Dev 19:229–238.
39.
Panopoulos ADO YanesS RuizYS KidaD DiepR TautenhahnA HerreriasEM BatchelderN Plongthongkum et al.2012. The metabolome of induced pluripotent stem cells reveals metabolic changes occurring in somatic cell reprogrammingCell Res22168-177. 39. Panopoulos AD, O Yanes, S Ruiz, YS Kida, D Diep, R Tautenhahn, A Herrerias, EM Batchelder, N Plongthongkum, et al. (2012). The metabolome of induced pluripotent stem cells reveals metabolic changes occurring in somatic cell reprogramming. Cell Res 22:168–177.
40.
Bodnar MSJJ MenesesRT RodriguezMT Firpo2004. Propagation and maintenance of undifferentiated human embryonic stem cellsStem Cells Dev13243-253. 40. Bodnar MS, JJ Meneses, RT Rodriguez and MT Firpo. (2004). Propagation and maintenance of undifferentiated human embryonic stem cells. Stem Cells Dev 13:243–253.
41.
Oliveros JC2007. VENNY an interactive tool for comparing lists with Venn Diagramshttp://bioinfogp.cnb.csic.es/tools/venny/index.htmlOctober112012. 41. Oliveros JC. (2007). VENNY an interactive tool for comparing lists with Venn Diagrams. http://bioinfogp.cnb.csic.es/tools/venny/index.html. Last accessed October 11, 2012.
42.
Ito MH HiramatsuK KobayashiK SuzueM KawahataK HiokiY UeyamaY KoyanagiK Sugamura et al.2002. NOD/SCID/gamma(c)(null) mouse: an excellent recipient mouse model for engraftment of human cellsBlood1003175-3182. 42. Ito M, H Hiramatsu, K Kobayashi, K Suzue, M Kawahata, K Hioki, Y Ueyama, Y Koyanagi, K Sugamura, et al. (2002). NOD/SCID/gamma(c)(null) mouse: an excellent recipient mouse model for engraftment of human cells. Blood 100:3175–3182.
43.
Thorpe WPJJ ReillySA Rosenberg1979. Prognostic significance of alkaline phosphatase measurements in patients with osteogenic sarcoma receiving chemotherapyCancer432178-2181. 43. Thorpe WP, JJ Reilly and SA Rosenberg. (1979). Prognostic significance of alkaline phosphatase measurements in patients with osteogenic sarcoma receiving chemotherapy. Cancer 43:2178–2181.
44.
Huang da WBT ShermanRA Lempicki2009. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene listsNucleic Acids Res371-13. 44. Huang da W, BT Sherman and RA Lempicki. (2009). Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37:1–13.
45.
Huang da WBT ShermanRA Lempicki2009. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resourcesNat Protoc444-57. 45. Huang da W, BT Sherman and RA Lempicki. (2009). Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44–57.
46.
Jensen LJM KuhnM StarkS ChaffronC CreeveyJ MullerT DoerksP JulienA Roth et al.2009. STRING 8—a global view on proteins and their functional interactions in 630 organismsNucleic Acids Res37D412-D416. 46. Jensen LJ, M Kuhn, M Stark, S Chaffron, C Creevey, J Muller, T Doerks, P Julien, A Roth, et al. (2009). STRING 8—a global view on proteins and their functional interactions in 630 organisms. Nucleic Acids Res 37:D412–D416.
47.
Huang JT ChenX LiuJ JiangJ LiD LiXS LiuW LiJ KangG Pei2009. More synergetic cooperation of Yamanaka factors in induced pluripotent stem cells than in embryonic stem cellsCell Res191127-1138. 47. Huang J, T Chen, X Liu, J Jiang, J Li, D Li, XS Liu, W Li, J Kang and G Pei. (2009). More synergetic cooperation of Yamanaka factors in induced pluripotent stem cells than in embryonic stem cells. Cell Res 19:1127–1138.
48.
Wei ZY YangP ZhangR AndrianakosK HasegawaJ LyuX ChenG BaiC LiuM PeraW Lu2009. Klf4 interacts directly with Oct4 and Sox2 to promote reprogrammingStem Cells272969-2978. 48. Wei Z, Y Yang, P Zhang, R Andrianakos, K Hasegawa, J Lyu, X Chen, G Bai, C Liu, M Pera and W Lu. (2009). Klf4 interacts directly with Oct4 and Sox2 to promote reprogramming. Stem Cells 27:2969–2978.
49.
Smith KNAM SinghS Dalton2010. Myc represses primitive endoderm differentiation in pluripotent stem cellsCell Stem Cell7343-354. 49. Smith KN, AM Singh and S Dalton. (2010). Myc represses primitive endoderm differentiation in pluripotent stem cells. Cell Stem Cell 7:343–354.
50.
Nakagawa MN TakizawaM NaritaT IchisakaS Yamanaka2010. Promotion of direct reprogramming by transformation-deficient MycProc Natl Acad Sci U S A10714152-14157. 50. Nakagawa M, N Takizawa, M Narita, T Ichisaka and S Yamanaka. (2010). Promotion of direct reprogramming by transformation-deficient Myc. Proc Natl Acad Sci U S A 107:14152–14157.
51.
Cotterman RVX JinSR KrigJM LemenA WeyPJ FarnhamPS Knoepfler2008. N-Myc regulates a widespread euchromatic program in the human genome partially independent of its role as a classical transcription factorCancer Res689654-9662. 51. Cotterman R, VX Jin, SR Krig, JM Lemen, A Wey, PJ Farnham and PS Knoepfler. (2008). N-Myc regulates a widespread euchromatic program in the human genome partially independent of its role as a classical transcription factor. Cancer Res 68:9654–9662.
52.
Knoepfler PSXY ZhangPF ChengPR GafkenSB McMahonRN Eisenman2006. Myc influences global chromatin structureEMBO J252723-2734. 52. Knoepfler PS, XY Zhang, PF Cheng, PR Gafken, SB McMahon and RN Eisenman. (2006). Myc influences global chromatin structure. EMBO J 25:2723–2734.
53.
Guccione EF MartinatoG FinocchiaroL LuziL TizzoniV Dall’ OlioG ZardoC NerviL BernardB Amati2006. Myc-binding-site recognition in the human genome is determined by chromatin contextNat Cell Biol8764-770. 53. Guccione E, F Martinato, G Finocchiaro, L Luzi, L Tizzoni, V Dall’ Olio, G Zardo, C Nervi, L Bernard and B Amati. (2006). Myc-binding-site recognition in the human genome is determined by chromatin context. Nat Cell Biol 8:764–770.
54.
Martinato FM CesaroniB AmatiE Guccione2008. Analysis of Myc-induced histone modifications on target chromatinPLoS One3e3650. 54. Martinato F, M Cesaroni, B Amati and E Guccione. (2008). Analysis of Myc-induced histone modifications on target chromatin. PLoS One 3:e3650.
55.
Werbowetski-Ogilvie TEA SchnerchS RampalliCE MillsJB LeeSH HongM Levadoux-MartinM Bhatia2011. Evidence for the transmission of neoplastic properties from transformed to normal human stem cellsOncogene304632-4644. 55. Werbowetski-Ogilvie TE, A Schnerch, S Rampalli, CE Mills, JB Lee, SH Hong, M Levadoux-Martin and M Bhatia. (2011). Evidence for the transmission of neoplastic properties from transformed to normal human stem cells. Oncogene 30:4632–4644.
56.
Felsher DWJM Bishop1999. Transient excess of MYC activity can elicit genomic instability and tumorigenesisProc Natl Acad Sci U S A963940-3944. 56. Felsher DW and JM Bishop. (1999). Transient excess of MYC activity can elicit genomic instability and tumorigenesis. Proc Natl Acad Sci U S A 96:3940–3944.
57.
Pera MF2011. Stem cells: the dark side of induced pluripotencyNature47146-47. 57. Pera MF. (2011). Stem cells: the dark side of induced pluripotency. Nature 471:46–47.
58.
Lin SLDC ChangS Chang-LinCH LinDT WuDT ChenSY Ying2008. Mir-302 reprograms human skin cancer cells into a pluripotent ES-cell-like stateRNA142115-2124. 58. Lin SL, DC Chang, S Chang-Lin, CH Lin, DT Wu, DT Chen and SY Ying. (2008). Mir-302 reprograms human skin cancer cells into a pluripotent ES-cell-like state. RNA 14:2115–2124.
59.
Miyoshi NH IshiiK NagaiH HoshinoK MimoriF TanakaH NaganoM SekimotoY DokiM Mori2009. Defined factors induce reprogramming of gastrointestinal cancer cellsProc Natl Acad Sci U S A10740-45. 59. Miyoshi N, H Ishii, K Nagai, H Hoshino, K Mimori, F Tanaka, H Nagano, M Sekimoto, Y Doki and M Mori. (2009). Defined factors induce reprogramming of gastrointestinal cancer cells. Proc Natl Acad Sci U S A 107:40–45.
60.
Sun CYK Liu2011. Induced pluripotent cancer cells: progress and applicationJ Cancer Res Clin Oncol1371-8. 60. Sun C and YK Liu. (2011). Induced pluripotent cancer cells: progress and application. J Cancer Res Clin Oncol 137:1–8.
61.
Cheong HC LuT LindstenCB Thompson2012. Therapeutic targets in cancer cell metabolism and autophagyNature Biotechnology30671-678. 61. Cheong H, C Lu, T Lindsten, CB Thompson. (2012). Therapeutic targets in cancer cell metabolism and autophagy. Nature Biotechnology 30:671–678.
Information & Authors
Information
Published In
Stem Cells and Development
Volume 22 • Issue Number 1 • January 1, 2013
Pages: 37 - 50
PubMed: 22998387
Copyright
Copyright 2013, Mary Ann Liebert, Inc.
History
Published in print: January 1, 2013
Published ahead of print: 26 October 2012
Published online: 21 September 2012
Accepted: 11 September 2012
Received: 5 July 2012
Topics
Authors
Author Disclosure Statement
No competing financial interests exist.
Metrics & Citations
Metrics
Citations
Export Citation
Export citation
Select the format you want to export the citations of this publication.
View Options
Access content
To read the fulltext, please use one of the options below to sign in or purchase access.⚠ Society Access
If you are a member of a society that has access to this content please log in via your society website and then return to this publication.