The cell cycle and pluripotency

Biochemical Journal

Volumn 451, Issue 2, 2013, Pages 135-143

  Hindley, Christopher ^a   Philpott, Anna ^b  

^a UNIVERSITY OF FREIBURG   (Germany)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

Cell cycle; Myc; Pluripotency; S phase

Indexed keywords

CYCLIN A; CYCLIN D; CYCLIN DEPENDENT KINASE 2; CYCLIN E; DNA METHYLTRANSFERASE 1; TRANSCRIPTION FACTOR GATA 6; TRANSCRIPTION FACTOR NANOG;

ANIMAL; CELL CYCLE; CELL CYCLE G1 PHASE; CELL CYCLE M PHASE; CELL CYCLE PROGRESSION; CELL CYCLE REGULATION; CELL CYCLE S PHASE; CELL DIVISION; CELL GROWTH; CELLULAR PARAMETERS; CHROMOSOME SEGREGATION; DNA METHYLATION; DNA SYNTHESIS; EUKARYOTIC CELL; NUCLEAR REPROGRAMMING; PLURIPOTENCY; PLURIPOTENT STEM CELL; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; REGULATORY MECHANISM; REVIEW; SOMATIC CELL;

ANIMALS; CELL CYCLE; CELL DIFFERENTIATION; EMBRYONIC STEM CELLS; GENES, MYC; HUMANS; MICE; PLURIPOTENT STEM CELLS;

EID: 84875591804     PISSN: 02646021     EISSN: 14708728     Source Type: Journal    
DOI: 10.1042/BJ20121627     Document Type: Review

References (97)

1. Murray, A. W. and Hunt, T. (1993) The Cell Cycle: an Introduction, Oxford University Press, Oxford
2. Sherr, C. J. and Roberts, J. M. (1999) CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev. 13, 1501-1512
3. Stead, E., White, J., Faast, R., Conn, S., Goldstone, S., Rathjen, J., Dhingra, U., Rathjen, P., Walker, D. and Dalton, S. (2002) Pluripotent cell division cycles are driven by ectopic Cdk2, cyclin A/E and E2F activities. Oncogene 21, 8320-8333
4. Lawson, K. A., Meneses, J. J. and Pedersen, R. A. (1991) Clonal analysis of epiblast fate during germ layer formation in the mouse embryo. Development 113, 891-911
5. Singh, A. M. and Dalton, S. (2009) The cell cycle and Myc intersect with mechanisms that regulate pluripotency and reprogramming. Cell Stem Cell 5, 141-149
6. Ballabeni, A., Park, I. H., Zhao, R., Wang, W., Lerou, P. H., Daley, G. Q. and Kirschner, M. W. (2011) Cell cycle adaptations of embryonic stem cells. Proc. Natl. Acad. Sci. U.S.A. 108, 19252-19257
7. White, J., Stead, E., Faast, R., Conn, S., Cartwright, P. and Dalton, S. (2005) Developmental activation of the Rb-E2F pathway and establishment of cell cycle-regulated cyclin-dependent kinase activity during embryonic stem cell differentiation. Mol. Biol. Cell 16, 2018-2027
8. Filipczyk, A. A., Laslett, A. L., Mummery, C. and Pera, M. F. (2007) Differentiation is coupled to changes in the cell cycle regulatory apparatus of human embryonic stem cells. Stem Cell Res. 1, 45-60
9. Dalton, S. (2009) Exposing hidden dimensions of embryonic stem cell cycle control. Cell Stem Cell 4, 9-10
10. Ohtsuka, S. and Dalton, S. (2008) Molecular and biological properties of pluripotent embryonic stem cells. Gene Ther. 15, 74-81
11. Newport, J. and Kirschner, M. (1982) A major developmental transition in early Xenopus embryos: I. characterization and timing of cellular changes at the midblastula stage. Cell 30, 675-686
12. Saka, Y. and Smith, J. C. (2001) Spatial and temporal patterns of cell division during early Xenopus embryogenesis. Dev. Biol. 229, 307-318
13. Vernon, A. E. and Philpott, A. (2003) A single cdk inhibitor, p27Xic1, functions beyond cell cycle regulation to promote muscle differentiation in Xenopus. Development 130, 71-83
14. Bloom, J. and Cross, F. R. (2007) Multiple levels of cyclin specificity in cell-cycle control. Nat. Rev. 8, 149-160
15. Santamaria, D., Barriere, C., Cerqueira, A., Hunt, S., Tardy, C., Newton, K., Caceres, J. F., Dubus, P., Malumbres, M. and Barbacid, M. (2007) Cdk1 is sufficient to drive the mammalian cell cycle. Nature 448, 811-815
16. Sherr, C. J. and Roberts, J. M. (2004) Living with or without cyclins and cyclin-dependent kinases. Genes Dev. 18, 2699-2711
17. Hartley, R. S., Rempel, R. E. and Maller, J. L. (1996) In vivo regulation of the early embryonic cell cycle in Xenopus. Dev. Biol. 173, 408-419
18. Buecker, C. and Geijsen, N. (2010) Different flavors of pluripotency, molecular mechanisms, and practical implications. Cell Stem Cell 7, 559-564
19. Ben-David, U., Kopper, O. and Benvenisty, N. (2012) Expanding the boundaries of embryonic stem cells. Cell Stem Cell 10, 666-677
20. Nichols, J. and Smith, A. (2009) Naive and primed pluripotent states. Cell Stem Cell 4, 487-492
21. Macfarlan, T. S., Gifford, W. D., Driscoll, S., Lettieri, K., Rowe, H. M., Bonanomi, D., Firth, A., Singer, O., Trono, D. and Pfaff, S. L. (2012) Embryonic stem cell potency fluctuates with endogenous retrovirus activity. Nature 487, 57-63
22. Van Hoof, D., Munoz, J., Braam, S. R., Pinkse, M. W., Linding, R., Heck, A. J., Mummery, C. L. and Krijgsveld, J. (2009) Phosphorylation dynamics during early differentiation of human embryonic stem cells. Cell Stem Cell 5, 214-226
23. Maimets, T., Neganova, I., Armstrong, L. and Lako, M. (2008) Activation of p53 by nutlin leads to rapid differentiation of human embryonic stem cells. Oncogene 27, 5277-5287
24. Gross, I., Lhermitte, B., Domon-Dell, C., Duluc, I., Martin, E., Gaiddon, C., Kedinger, M. and Freund, J. N. (2005) Phosphorylation of the homeotic tumor suppressor Cdx2 mediates its ubiquitin-dependent proteasome degradation. Oncogene 24, 7955-7963
25. Neganova, I., Zhang, X., Atkinson, S. and Lako, M. (2009) Expression and functional analysis of G1 to S regulatory components reveals an important role for CDK2 in cell cycle regulation in human embryonic stem cells. Oncogene 28, 20-30
26. Deshpande, A. M., Dai, Y. S., Kim, Y., Kim, J., Kimlin, L., Gao, K. and Wong, D. T. (2009) Cdk2ap1 is required for epigenetic silencing of Oct4 during murine embryonic stem cell differentiation. J. Biol. Chem. 284, 6043-6047
27. Kim, Y., McBride, J., Kimlin, L., Pae, E. K., Deshpande, A. and Wong, D. T. (2009) Targeted inactivation of p12, CDK2 associating protein 1, leads to early embryonic lethality. PLoS ONE 4, e4518
28. Zhang, X., Neganova, I., Przyborski, S., Yang, C., Cooke, M., Atkinson, S. P., Anyfantis, G., Fenyk, S., Keith, W. N., Hoare, S. F. et al. (2009) A role for NANOG in G1 to S transition in human embryonic stem cells through direct binding of CDK6 and CDC25A. J. Cell Biol. 184, 67-82
29. Savatier, P., Lapillonne, H., Jirmanova, L., Vitelli, L. and Samarut, J. (2002) Analysis of the cell cycle in mouse embryonic stem cells. Methods Mol. Biol. 185, 27-33
30. Madine, M. and Laskey, R. (2001) Geminin bans replication licence. Nat. Cell Biol. 3, E49-E50
31. McGarry, T. J. and Kirschner, M. W. (1998) Geminin, an inhibitor of DNA replication, is degraded during mitosis. Cell 93, 1043-1053
32. Seo, S. and Kroll, K. L. (2006) Geminin's double life: chromatin connections that regulate transcription at the transition from proliferation to differentiation. Cell Cycle 5, 374-379
33. Gonzalez, M. A., Tachibana, K. E., Adams, D. J., van der Weyden, L., Hemberger, M., Coleman, N., Bradley, A. and Laskey, R. A. (2006) Geminin is essential to prevent endoreduplication and to form pluripotent cells during mammalian development. Genes Dev. 20, 1880-1884
34. Yang, V. S., Carter, S. A., Hyland, S. J., Tachibana-Konwalski, K., Laskey, R. A. and Gonzalez, M. A. (2011) Geminin escapes degradation in G1 of mouse pluripotent cells and mediates the expression of Oct4, Sox2, and Nanog. Curr. Biol. 21, 692-699
35. Ohno, Y., Yasunaga, S., Ohtsubo, M., Mori, S., Tsumura, M., Okada, S., Ohta, T., Ohtani, K., Kobayashi, M. and Takihara, Y. (2010) Hoxb4 transduction down-regulates Geminin protein, providing hematopoietic stem and progenitor cells with proliferation potential. Proc. Natl. Acad. Sci. U.S.A. 107, 21529-21534
36. Shinnick, K. M., Eklund, E. A. and McGarry, T. J. (2010) Geminin deletion from hematopoietic cells causes anemia and thrombocytosis in mice. J. Clin. Invest. 120, 4303-4315
37. Gaspar-Maia, A., Alajem, A., Meshorer, E. and Ramalho-Santos, M. (2011) Open chromatin in pluripotency and reprogramming. Nat. Rev. Mol. Cell Biol. 12, 36-47
38. Meissner, A., Mikkelsen, T. S., Gu, H., Wernig, M., Hanna, J., Sivachenko, A., Zhang, X., Bernstein, B. E., Nusbaum, C., Jaffe, D. B. et al. (2008) Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature 454, 766-770
39. Bernstein, B. E., Mikkelsen, T. S., Xie, X., Kamal, M., Huebert, D. J., Cuff, J., Fry, B., Meissner, A., Wernig, M., Plath, K. et al. (2006) A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125, 315-326
40. Efroni, S., Duttagupta, R., Cheng, J., Dehghani, H., Hoeppner, D. J., Dash, C., Bazett-Jones, D. P., Le Grice, S., McKay, R. D., Buetow, K. H. et al. (2008) Global transcription in pluripotent embryonic stem cells. Cell Stem Cell 2, 437-447
41. Lavoie, G. and St-Pierre, Y. (2011) Phosphorylation of human DNMT1: implication of cyclin-dependent kinases. Biochem. Biophys. Res. Commun. 409, 187-192
42. Hale, T. K., Contreras, A., Morrison, A. J. and Herrera, R. E. (2006) Phosphorylation of the linker histone H1 by CDK regulates its binding to HP1α. Mol. Cell 22, 693-699
43. Terme, J. M., Seśe, B., Milĺan-Arino, L., Mayor, R., Izpiśua Belmonte, J. C., Barrero, M. J. and Jordan, A. (2011) Histone H1 variants are differentially expressed and incorporated into chromatin during differentiation and reprogramming to pluripotency. J. Biol. Chem. 286, 35347-35357
44. Brown, D. T. (2003) Histone H1 and the dynamic regulation of chromatin function. Biochem. Cell Biol. 81, 221-227
45. Zhang, Y., Cooke, M., Panjwani, S., Cao, K., Krauth, B., Ho, P. Y., Medrzycki, M., Berhe, D. T., Pan, C., McDevitt, T. C. et al. (2012) Histone H1 depletion impairs embryonic stem cell differentiation. PLoS Genet. 8, e1002691
46. Freedman, B. S. and Heald, R. (2010) Functional comparison of H1 histones in Xenopus reveals isoform-specific regulation by Cdk1 and RanGTP. Curr. Biol. 20, 1048-1052
47. Osley, M. A. (1991) The regulation of histone synthesis in the cell cycle. Annu. Rev. Biochem. 60, 827-861
48. Smith, S. and Stillman, B. (1991) Stepwise assembly of chromatin during DNA replication in vitro. EMBO J. 10, 971-980
49. Philpott, A., Krude, T. and Laskey, R. A. (2000) Nuclear chaperones. Semin. Cell Dev. Biol. 11, 7-14
50. Verreault, A. (2000) De novo nucleosome assembly: new pieces in an old puzzle. Genes Dev. 14, 1430-1438
51. Petruk, S., Sedkov, Y., Johnston, D. M., Hodgson, J. W., Black, K. L., Kovermann, S. K., Beck, S., Canaani, E., Brock, H. W. and Mazo, A. (2012) TrxG and PcG proteins but not methylated histones remain associated with DNA through replication. Cell 150, 922-933
52. Aoto, T., Saitoh, N., Sakamoto, Y., Watanabe, S. and Nakao, M. (2008) Polycomb group protein-associated chromatin is reproduced in post-mitotic G1 phase and is required for S phase progression. J. Biol. Chem. 283, 18905-18915
53. Laskey, R. A. and Gurdon, J. B. (1970) Genetic content of adult somatic cells tested by nuclear transplantation from cultured cells. Nature 228, 1332-1334
54. Briggs, R. and King, T. J. (1952) Transplantation of living nuclei from blastula cells into enucleated frogs' eggs. Proc. Natl. Acad. Sci. U.S.A. 38, 455-463
55. Gurdon, J. B., Elsdale, T. R. and Fischberg, M. (1958) Sexually mature individuals of Xenopus laevis from the transplantation of single somatic nuclei. Nature 182, 64-65
56. Takahashi, K. and Yamanaka, S. (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663-676
57. Buganim, Y., Faddah, D. A., Cheng, A. W., Itskovich, E., Markoulaki, S., Ganz, K., Klemm, S. L., van Oudenaarden, A. and Jaenisch, R. (2012) Single-cell expression analyses during cellular reprogramming reveal an early stochastic and a late hierarchic phase. Cell 150, 1209-1222
58. Hanna, J., Saha, K., Pando, B., van Zon, J., Lengner, C. J., Creyghton, M. P., van Oudenaarden, A. and Jaenisch, R. (2009) Direct cell reprogramming is a stochastic process amenable to acceleration. Nature 462, 595-601
59. Stadtfeld, M., Maherali, N., Breault, D. T. and Hochedlinger, K. (2008) Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse. Cell Stem Cell 2, 230-240
60. Huangfu, D., Maehr, R., Guo, W., Eijkelenboom, A., Snitow, M., Chen, A. E. and Melton, D. A. (2008) Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat. Biotechnol. 26, 795-797
61. Maherali, N., Sridharan, R., Xie, W., Utikal, J., Eminli, S., Arnold, K., Stadtfeld, M., Yachechko, R., Tchieu, J., Jaenisch, R. et al. (2007) Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell 1, 55-70
62. Sridharan, R., Tchieu, J., Mason, M. J., Yachechko, R., Kuoy, E., Horvath, S., Zhou, Q. and Plath, K. (2009) Role of the murine reprogramming factors in the induction of pluripotency. Cell 136, 364-377
63. Hanna, J., Markoulaki, S., Schorderet, P., Carey, B. W., Beard, C., Wernig, M., Creyghton, M. P., Steine, E. J., Cassady, J. P., Foreman, R. et al. (2008) Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. Cell 133, 250-264
64. Cobaleda, C., Jochum, W. and Busslinger, M. (2007) Conversion of mature B cells into T cells by dedifferentiation to uncommitted progenitors. Nature 449, 473-477
65. Weintraub, H., Tapscott, S. J., Davis, R. L., Thayer, M. J., Adam, M. A., Lassar, A. B. and Miller, A. D. (1989) Activation of muscle-specific genes in pigment, nerve, fat, liver, and fibroblast cell lines by forced expression of MyoD. Proc. Natl. Acad. Sci. U.S.A. 86, 5434-5438
66. Warren, L., Manos, P. D., Ahfeldt, T., Loh, Y. H., Li, H., Lau, F., Ebina, W., Mandal, P. K., Smith, Z. D., Meissner, A. et al. (2010) Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell 7, 618-630
67. Ganier, O., Bocquet, S., Peiffer, I., Brochard, V., Arnaud, P., Puy, A., Jouneau, A., Feil, R., Renard, J. P. andḾechali, M. (2011) Synergic reprogramming of mammalian cells by combined exposure to mitotic Xenopus egg extracts and transcription factors. Proc. Natl. Acad. Sci. U.S.A. 108, 17331-17336
68. Egli, D., Birkhoff, G. and Eggan, K. (2008) Mediators of reprogramming: transcription factors and transitions through mitosis. Nat. Rev. Mol. Cell Biol. 9, 505-516
69. Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K. and Yamanaka, S. (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131, 861-872
70. Edel, M. J., Menchon, C., Menendez, S., Consiglio, A., Raya, A. and Izpisua Belmonte, J. C. (2010) Rem2 GTPase maintains survival of human embryonic stem cells as well as enhancing reprogramming by regulating p53 and cyclin D1. Genes Dev. 24, 561-573
71. Medina, R., Ghule, P. N., Cruzat, F., Barutcu, A. R., Montecino, M., Stein, J. L., van Wijnen, A. J. and Stein, G. S. (2012) Epigenetic control of cell cycle-dependent histone gene expression is a principal component of the abbreviated pluripotent cell cycle. Mol. Cell. Biol. 32, 3860-3871
72. Li, H., Collado, M., Villasante, A., Strati, K., Ortega, S., Canamero, M., Blasco, M. A. and Serrano, M. (2009) The Ink4/Arf locus is a barrier for iPS cell reprogramming. Nature 460, 1136-1139
73. Kawamura, T., Suzuki, J., Wang, Y. V., Menendez, S., Morera, L. B., Raya, A., Wahl, G. M. and Izpiśua Belmonte, J. C. (2009) Linking the p53 tumour suppressor pathway to somatic cell reprogramming. Nature 460, 1140-1144
74. Ruiz, S., Panopoulos, A. D., Herreŕias, A., Bissig, K. D., Lutz, M., Berggren, W. T., Verma, I. M. and Izpisua Belmonte, J. C. (2011) A high proliferation rate is required for cell reprogramming and maintenance of human embryonic stem cell identity. Curr. Biol. 21, 45-52
75. Agami, R. and Bernards, R. (2000) Distinct initiation and maintenance mechanisms cooperate to induce G1 cell cycle arrest in response to DNA damage. Cell 102, 55-66
76. Meyer, N. and Penn, L. Z. (2008) Reflecting on 25 years with MYC. Nat. Rev. Cancer 8, 976-990
77. Reference deleted 78 Hanna, J., Markoulaki, S., Mitalipova, M., Cheng, A. W., Cassady, J. P., Staerk, J., Carey, B. W., Lengner, C. J., Foreman, R., Love, J. et al. (2009) Metastable pluripotent states in NOD-mouse-derived ESCs. Cell Stem Cell 4, 513-524
78. Baudino, T. A., McKay, C., Pendeville-Samain, H., Nilsson, J. A., Maclean, K. H., White, E. L., Davis, A. C., Ihle, J. N. and Cleveland, J. L. (2002) c-Myc is essential for vasculogenesis and angiogenesis during development and tumor progression. Genes Dev. 16, 2530-2543
79. Smith, K. N., Singh, A. M. and Dalton, S. (2010) Myc represses primitive endoderm differentiation in pluripotent stem cells. Cell Stem Cell 7, 343-354
80. Smith, K. N., Lim, J. M., Wells, L. and Dalton, S. (2011) Myc orchestrates a regulatory network required for the establishment and maintenance of pluripotency. Cell Cycle 10, 592-597
81. Wilson, A., Murphy, M. J., Oskarsson, T., Kaloulis, K., Bettess, M. D., Oser, G. M., Pasche, A. C., Knabenhans, C., Macdonald, H. R. and Trumpp, A. (2004) c-Myc controls the balance between hematopoietic stem cell self-renewal and differentiation. Genes Dev. 18, 2747-2763
82. Lo Celso, C., Berta, M. A., Braun, K. M., Frye, M., Lyle, S., Zouboulis, C. C. and Watt, F. M. (2008) Characterization of bipotential epidermal progenitors derived from human sebaceous gland: contrasting roles of c-Myc and β-catenin. Stem Cells 26, 1241-1252
83. Watt, F. M., Frye, M. and Benitah, S. A. (2008) MYC in mammalian epidermis: how can an oncogene stimulate differentiation Nat. Rev. Cancer 8, 234-242
84. Lin, C. H., Lin, C., Tanaka, H., Fero, M. L. and Eisenman, R. N. (2009) Gene regulation and epigenetic remodeling in murine embryonic stem cells by c-Myc. PLoS ONE 4, -e7839
85. Fernandez, P. C., Frank, S. R., Wang, L., Schroeder, M., Liu, S., Greene, J., Cocito, A. and Amati, B. (2003) Genomic targets of the human c-Myc protein. Genes Dev. 17, 1115-1129
86. Guccione, E., Martinato, F., Finocchiaro, G., Luzi, L., Tizzoni, L., Dall' Olio, V., Zardo, G., Nervi, C., Bernard, L. and Amati, B. (2006) Myc-binding-site recognition in the human genome is determined by chromatin context. Nat. Cell Biol. 8, 764-770
87. Chen, X., Xu, H., Yuan, P., Fang, F., Huss, M., Vega, V. B., Wong, E., Orlov, Y. L., Zhang, W., Jiang, J. et al. (2008) Integration of external signaling pathways with the core transcriptional network in embryonic stem cells. Cell 133, 1106-1117
88. Kim, J., Chu, J., Shen, X., Wang, J. and Orkin, S. H. (2008) An extended transcriptional network for pluripotency of embryonic stem cells. Cell 132, 1049-1061
89. Kidder, B. L., Yang, J. and Palmer, S. (2008) Stat3 and c-Myc genome-wide promoter occupancy in embryonic stem cells. PLoS ONE 3, e3932
90. Judson, R. L., Babiarz, J. E., Venere, M. and Blelloch, R. (2009) Embryonic stem cell-specific microRNAs promote induced pluripotency. Nat. Biotechnol. 27, 459-461
91. Araki, R., Hoki, Y., Uda, M., Nakamura, M., Jincho, Y., Tamura, C., Sunayama, M., Ando, S., Sugiura, M., Yoshida, M. A. et al. (2011) Crucial role of c-Myc in the generation of induced pluripotent stem cells. Stem Cells 29, 1362-1370
92. Li, H. Y., Chien, Y., Chen, Y. J., Chen, S. F., Chang, Y. L., Chiang, C. H., Jeng, S. Y., Chang, C. M., Wang, M. L., Chen, L. K. et al. (2011) Reprogramming induced pluripotent stem cells in the absence of c-Myc for differentiation into hepatocyte-like cells. Biomaterials 32, 5994-6005
93. Nakagawa, M., Koyanagi, M., Tanabe, K., Takahashi, K., Ichisaka, T., Aoi, T., Okita, K., Mochiduki, Y., Takizawa, N. and Yamanaka, S. (2008) Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat. Biotechnol. 26, 101-106
94. Nakagawa, M., Takizawa, N., Narita, M., Ichisaka, T. and Yamanaka, S. (2010) Promotion of direct reprogramming by transformation-deficient Myc. Proc. Natl. Acad. Sci. U.S.A. 107, 14152-14157
95. Reference deleted 97 Wernig, M., Meissner, A., Cassady, J. P. and Jaenisch, R. (2008) c-Myc is dispensable for direct reprogramming of mouse fibroblasts. Cell Stem Cell 2, 10-12
96. Ring, K. L., Tong, L. M., Balestra, M. E., Javier, R., Andrews-Zwilling, Y., Li, G., Walker, D., Zhang, W. R., Kreitzer, A. C. and Huang, Y. (2012) Direct reprogramming of mouse and human fibroblasts into multipotent neural stem cells with a single factor. Cell Stem Cell 11, 100-109
97. Roccio, M., Schmitter, D., Knobloch, M., Okawa, Y., Sage, D. and Lutolf, M. P. (2013) Predicting stem cell fate changes by differential cell cycle progression patterns. Development 140, 459-470