1. College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China;; 2. Anhui Provincial Animals Genetic Resources Conservation Center, Hefei 231283, China
Pluripotent stem cells (PSCs), characterized by being able to differentiate into various types of cells, are generally regarded as the most promising sources for cell replacement therapies. However, as typical PSCs, embryonic stem cells (ESCs) are still far away from human clinics so far due to ethical issues and immune rejection response. One way to avoid such problems is to use stem cells derived from autologous somatic cells. Up to date, PSCs could be obtained by reprogramming somatic cells to pluripotent state with approaches including somatic cell nuclear transfer (SCNT), fusion with stem cells, coculture with cells’ extracts, and induction with defined factors. Among these, through reprogramming somatic cells directly by retroviral transduction of transcription factors, induced pluripotent stem (iPS) cells have been successfully generated in both mouse and human recently. These iPS cells shared similar morphology and growth properties to ESCs, could express ESCs marker genes, and could produce adult or germline-competent chimaeras and differentiate into a variety of cell types, including germ cells. Moreover, with iPS technique, patient specific PSCs could be derived more easily from handful somatic cells in human without immune rejection responses innately connected to ESCs. Consequently, generation of iPS cells would be of great help to further understand disease mechanisms, drug screening, and cell transplantation therapies as well. In summary, the recent progress in the study of cell reprogramming for the creation of patient-specific pluripotent stem cells, some existing problems, and research perspectives were suggested.
. Cell reprogramming for the creation of patient-specific pluripotent stem cells by defined factors[J]. Frontiers of Agriculture in China, 2009, 3(2): 199-208.
Huiqun YIN, Hongguo CAO, Yunhai ZHANG, Yong TAO, Xiaorong ZHANG, Heng WANG. Cell reprogramming for the creation of patient-specific pluripotent stem cells by defined factors. Front Agric Chin, 2009, 3(2): 199-208.
Adhikary S, Eilers M (2005). Transcriptional regulation and transformation by Myc proteins. Nat Rev Mol Cell Biol , 6: 635-645 doi: 10.1038/nrm1703
2
Alon U (2007). Network motifs: theory and experimental approaches. Nat Rev Genet , 8: 450-461 doi: 10.1038/nrg2102
3
Aoi T, Yae K, Nakagawa M, Ichisaka T, Okita K, Takahashi K, Chiba T, Yamanaka S (2008). Generation of pluripotent stem cells from adult mouse liver and stomach cells. Science , 321(5889): 699-702 doi: 10.1126/science.1154884
4
Blelloch R, Venere M, Yen J, Ramalho-Santos M (2007). Generation of induced pluripotent stem cells in the absence of drug selection. Cell Stem Cell , 1: 245-247 doi: 10.1016/j.stem.2007.08.008
5
Boyer L A, Lee T I, Cole M F, Johnstone S E, Levine S S, Zucker J P, Guenther M G, Kumar R M, Murray H L, Jenner R G, Gifford D K, Melton D A, Jaenisch R, Young R A (2005). Core transcriptional regulatory circuitry in human embryonic stem cells. Cell , 122: 947-956 doi: 10.1016/j.cell.2005.08.020
6
Brambrink T, Foreman R, Welstead G G, Lengner C J, Wernig M, Suh H, Jaenisch R (2008). Sequential expression of pluripotency markers during direct reprogramming of mouse somatic cells. Cell Stem Cell , 2: 151-159 doi: 10.1016/j.stem.2008.01.004
7
Bru T, Clarke C, McGrew M J, Sang H M, Wilmut I, Blow J J (2008). Rapid induction of pluripotency genes after exposure of human somatic cells to mouse ES cell extracts. Exp Cell Res , 314(14): 2634-2642 doi: 10.1016/j.yexcr.2008.05.009
8
Cartwright P, McLean C, Sheppard A, Rivett D, Jones K, Dalton S (2005). LIF/STAT3 controls ES cell self-renewal and pluripotency by a Myc-dependent mechanism. Development , 132: 885-896 doi: 10.1242/dev.01670
9
Cawley S, Bekiranov S, Ng H H, Kapranov P, Sekinger E A, Kampa D, Piccolboni A, Sementchenko V, Cheng J, Williams A J, Wheeler R, Wong B, Drenkow J, Yamanaka M, Patel S, Brubaker S, Tammana H, Helt G, Struhl K, Gingeras T R (2004). Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs. Cell , 116: 499-509 doi: 10.1016/S0092-8674(04)00127-8
10
Collas P, Taranger C K (2006a). Toward reprogramming cells to pluripotency. Ernst Schering Res Found Workshop , 60: 47-67 doi: 10.1007/3-540-31437-7_5
11
Collas P, Taranger C K (2006b). Epigenetic reprogramming of nuclei using cell extracts. Stem Cell Rev , 2: 309-317 doi: 10.1007/BF02698058
12
Collas P, Taranger C K, Boquest A C, Noer A, Dahl J A (2006). On the way to reprogramming cells to pluripotency using cell-free extracts. Reproductive Bio Medicine , 12: 762-770
13
Cowan C A, Atienza J, Melton D A, Eggan K (2005). Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells. Science , 309: 1369-1373 doi: 10.1126/science.1116447
14
Darr H, Benvenisty N (2006). Factors involved in self-renewal and pluripotency of embryonic stem cells. Handb Exp Pharmacol , 174: 1-19
15
Dimos J T, Rodolfa K T, Niakan K K, Weisenthal L M, Mitsumoto H, Chung W, Croft G F, Saphier G, Leibel R, Goland R, Wichterle H, Henderson C E, Eggan K (2008). Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science , 321(5893): 1218-1221 doi: 10.1126/science.1158799
16
Dominguez-Sola D, Ying C Y, Grandori C, Ruggiero L, Chen B, Li M, Galloway D A, Gu W, Gautier J, Dalla-Favera R (2007). Nontranscriptional control of DNA replication by c-Myc. Nature , 448: 445-451 doi: 10.1038/nature05953
17
Fong H, Hohenstein K A, Donovan P J (2008). Regulation of Self-renewal and pluripotency by Sox2 in human embryonic stem cells. Stem Cells , 26(8): 1931-1938 doi: 10.1634/stemcells.2007-1002
18
Grinnemo K H, Sylvén C, Hovatta O, Dellgren G, Corbascio M (2008). Immunogenicity of human embryonic stem cells. Cell Tissue Res , 331: 67-78 doi: 10.1007/s00441-007-0486-3
19
Hanna J, Markoulaki S, Schorderet P, Carey B W, Beard C, Wernig M, Creyghton M P, Steine E J, Cassady J P, Foreman R, Lengner C J, Dausman J A, Jaenisc R (2008). Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. Cell , 133: 250-264 doi: 10.1016/j.cell.2008.03.028
20
Hanna J, Wernig M, Markoulaki S, Sun C W, Meissner A, Cassady J P, Beard C, Brambrink T, Wu L C, Townes T M, Jaenisch R (2007). Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science , 318: 1920-1923
21
Hansis C, Barreto G, Maltry N, Niehrs C (2004). Nuclear reprogramming of human somatic cells by xenopus egg extract requires BRG1. Curr Biol , 14: 1475-1480 doi: 10.1016/j.cub.2004.08.031
22
Harley V R, Lovell-Badge R, Goodfellow P N (1994). Definition of a consensus DNA binding site for SRY. Nucleic Acids Res , 22: 1500-1501 doi: 10.1093/nar/22.8.1500
23
Hochedlinger K, Jaenisch R (2006). Nuclear reprogramming and pluripotency. Nature , 441: 1061-1067 doi: 10.1038/nature04955
24
Jaenisch R, Young R (2002). Myc suppression of the p21 (Cip1) Cdk inhibitor influences the outcome of the p53 response to DNA damage. Nature , 419: 729-734 doi: 10.1038/nature01119
25
Jaenisch R, Young R (2008). Stem cells, the molecular circuitry of pluripotency and nuclear reprogramming. Cell , 132: 567-582 doi: 10.1016/j.cell.2008.01.015
26
Jiang J, Chan Y S, Loh Y H, Cai J, Tong G Q, Lim C A, Robson P, Zhong S, Ng H H (2008). A core Klf circuitry regulates self-renewal of embryonic stem cells. Nat Cell Biol , 10: 353-360 doi: 10.1038/ncb1698
27
Kfoury C (2007). Therapeutic cloning: promises and issues. Mcgill J Med , 10: 112-120
28
Kim J B, Zaehres H, Wu G, Gentile L, Ko K, Sebastiano V, Araúzo-Bravo M J, Ruau D, Han D W, Zenke M, Sch?ler H R (2008). Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature , 454(7204): 646-650 doi: 10.1038/nature07061
29
Klimanskaya I, Rosenthal N, Lanza R (2008). Derive and conquer: sourcing and differentiating stem cells for therapeutic applications. Nat Rev Drug Discov , 7: 131-142 doi: 10.1038/nrd2403
30
Knoepfler P S, Zhang X Y, Cheng P F, Gafken P R, McMahon S B, Eisenman R N (2006). Myc influences global chromatin structure. EMBO J , 25: 2723-2734 doi: 10.1038/sj.emboj.7601152
31
Kohda T, Inoue K, Ogonuki N, Miki H, Naruse M, Kaneko-Ishino T, Ogura A, Ishino F (2005). Variation in gene expression and aberrantly regulated chromosome regions in cloned mice. Biol Reprod , 73: 1302-1311 doi: 10.1095/biolreprod.105.044958
32
Lagarkova M A, Volchkov P Y, Lyakisheva A V, Philonenko E S, Kiselev S L (2006). Diverse epigenetic profile of novel human embryonic stem cell lines. Cell Cycle , 5: 416-420
33
Li Y, McClintick J, Zhong L, Edenberg H J, Yoder M C, Chan R J (2005). Murine embryonic stem cell differentiation is promoted by SOCS-3 and inhibited by the zinc finger transcription factor Klf4. Blood , 105: 635-637 doi: 10.1182/blood-2004-07-2681
34
Liao J, Wu Z, Wang Y, Cheng L, Cui C, Gao Y, Chen T, Rao L, Chen, S, Jia N, Dai H, Xin S, Kang J, Pei G, Xiao L (2008). Enhanced efficiency of generating induced pluripotent stem (iPS) cells from human somatic cells by a combination of six transcription factors. Cell Res , 18: 600-603 doi: 10.1038/cr.2008.51
35
Lin T, Chao C, Saito S, Mazur S J, Murphy M E, Appella E, Xu Y (2005). p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression. Nat Cell Bio , 7: 165-171 doi: 10.1038/ncb1211
36
Lowry W E, Richter L, Yachechko R, Pyle A D, Tchieu J, Sridharan R, Clark A T, Plath K (2008). Generation of human induced pluripotent stem cells from dermal fibroblasts. Proc Natl Acad Sci U S A , 105: 2883-2888 doi: 10.1073/pnas.0711983105
37
Maherali N, Sridharan R, Xie W, Utikal J, Eminli S, Arnold K, Stadtfeld M, Yachechko R, Tchieu J, Jaenisch R, Plath K, Hochedlinger K (2007). Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell , 1: 55-70 doi: 10.1016/j.stem.2007.05.014
38
Mali P, Ye Z, Hommond H H, Yu X, Lin J, Chen G, Zou J, Cheng L (2008). Improved efficiency and pace of generating induced pluripotent stem cells from human adult and fetal fibroblasts. Stem Cells , 26(8): 1998-2005 doi: 10.1634/stemcells.2008-0346
39
Matsumura H, Tada M, Otsuji T, Yasuchika K, Nakatsuji N, Surani A, Tada T (2007). Targeted chromosome elimination from ES-somatic hybrid cells. Nat Methods , 4: 23-25 doi: 10.1038/nmeth973
40
Meissner A, Wernig M, Jaenisch R (2007). Direct reprogramming of genetically unmodified fibroblasts into pluripotent stem cells. Nat Biotechnol , 25: 1177-1181 doi: 10.1038/nbt1335
41
Miller R A, Ruddle F H (1976). Pluripotent teratocarcinoma-thymus somatic cell hybrids, Cell , 9: 45-55 doi: 10.1016/0092-8674(76)90051-9
42
Nakagawa M, Koyanagi M, Tanabe K, Takahashi K, Ichisaka T, Aoi T, Okita K, Mochiduki Y, Takizawa N, Yamanaka S (2008). Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechno , 26: 101-106 doi: 10.1038/nbt1374
43
Nakatake Y, Fukui N, Iwamats Y, Masui S, Takahashi K, Yagi R, Yagi K, Miyazaki J, Matoba R, Ko M S, Niwa H (2006). Klf4 cooperates with Oct3/4 and Sox2 to activate the Lefty1 core promoter in embryonic stem cells. Mol Cell Biol , 26(20): 7772-7782 doi: 10.1128/MCB.00468-06
44
Neri T, Monti M, Rebuzzini P, Merico V, Garagna S, Redi C A, Zuccotti M (2007). Mouse fibroblasts are reprogrammed to Oct-4 and Rex-1 gene expression and alkaline phosphatase activity by embryonic stem cell extracts. Cloning Stem Cells , 9: 394-406 doi: 10.1089/clo.2006.0011
45
Okamoto K, Okazawa H, Okuda A, Sakai M, Muramatsu M, Hamada H (1990). A novel octamer binding transcription factor is differentially expressed in mouse embryonic cells. Cell , 60: 461-472 doi: 10.1016/0092-8674(90)90597-8
46
Okita K, Ichisaka T, Yamanaka S (2007). Generation of germline-competent induced pluripotent stem cells. Nature , 448: 313-317 doi: 10.1038/nature05934
47
Park I H, Daley G Q (2007). Debugging cellular reprogramming. Nat Cell Biol , 9: 871-873 doi: 10.1038/ncb0807-871
48
Park I H, Zhao R, West J A, Yabuuchi A, Huo H, Ince T A, Lerou P H, Lensch M W, Daley G Q (2008). Reprogramming of human somatic cells to pluripotency with defined factors. Nature , 451: 141-146 doi: 10.1038/nature06534
49
Pasquinelli A E, Hunter S, Bracht J (2005). MicroRNAs: a developing story. Curr Opin Genet Dev , 15: 200-205 doi: 10.1016/j.gde.2005.01.002
Pochampally R R, Neville B T, Schwarz E J, Li M M, Prockop D J (2004). Rat adult stem cells (marrow stromal cells) engraft and differentiate in chick embryos without evidence of cell fusion. Proc Natl Acad Sci U S A , 101: 9282-9285 doi: 10.1073/pnas.0401558101
52
Qin D, Li W, Zhang J, Pei D (2007). Direct generation of ES-like cells from unmodified mouse embryonic fibroblasts by Oct4/Sox2/Myc/Klf4. Cell Res , 17: 959-962 doi: 10.1038/cr.2007.92
53
Rosner M H, Vigano M A, Ozato K, Timmons P M, Poirier F, Rigby P W, Staudt L M (1990). A POU-domain transcription factor in early stem cells and germ cells of the mammalian embryo. Nature , 345: 686-692 doi: 10.1038/345686a0
54
Rowland B D, Bernards R, Peeper D S (2005). The KLF4 tumour suppressor is a transcriptional repressor of p53 that acts as a context-dependent oncogene. Nat Cell Biol , 7: 1074-1082 doi: 10.1038/ncb1314
55
Silva J, Chambers I, Pollard S, Smith A (2006). Nanog promotes transfer of pluripotency after cell fusion. Nature , 441: 997-1001 doi: 10.1038/nature04914
56
Smith S L, Everts R E, Tian X C, Du F, Sung L Y, Rodriguez-Zas S L, Jeong B S, Renard J P, Lewin H A, Yang X (2005). Global gene expression profiles reveal significant nuclear reprogramming by the blastocyst stage after cloning. Proc Natl Acad Sci U S A , 102: 17582-17587 doi: 10.1073/pnas.0508952102
57
Sonia S, Michel P (2007). Oct-3/4: Not just a gatekeeper of pluripotency for embryonic stem cell, a cell fate instructor through a gene dosage effect. Cell Cycle , 6: 8-10
58
Stadtfeld M, Brennand K, Hochedlinger K (2008b). Reprogramming of pancreatic Beta cells into induced pluripotent stem cells. Curr Biol , 18: 890-894 doi: 10.1016/j.cub.2008.05.010
59
Stadtfeld M, Maherali N, Breault D T, Hochedlinger K (2008a). Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse. Cell Stem Cell , 2: 230-240 doi: 10.1016/j.stem.2008.02.001
60
Tada M, Morizane A, Kimura H, Kawasaki H, Ainscough J F, Sasai Y, Nakatsuji N, Tada T (2003). Pluripotency of reprogrammed somatic genomes in embryonic stem hybrid cells. Dev Dyn , 227: 504-510 doi: 10.1002/dvdy.10337
61
Tada M, Tada T, Lefebvre L, Barton S C, Surani, M A (1997). Embryonic germ cells induce epigenetic reprogramming of somatic nucleus in hybrid cells. EMBO J , 16: 6510-6520 doi: 10.1093/emboj/16.21.6510
62
Takahashi K, Okita K, Nakagawa M, Yamanaka S (2007a). Induction of pluripotent stem cells from fibroblast cultures. Nat Protoc , 2: 3081-3089 doi: 10.1038/nprot.2007.418
63
Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007b). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell , 131: 861-872 doi: 10.1016/j.cell.2007.11.019
64
Takahashi K, Yamanaka S (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell , 126: 663-676 doi: 10.1016/j.cell.2006.07.024
65
Tateishi K, He J, Taranova O, Liang G, Liang G, D'Alessio A C, Zhang Y (2008). Generation of insulin-secreting islet-like clusters from human skin fibroblasts. J Biol Chem , 283(46): 31601-31607
66
Tokuzawa Y, Kaiho E, Maruyama M, Takahashi K, Mitsui K, Maeda M, Niwa H, Yamanaka S (2003). Fbx15 is a novel target of Oct3/4 but is dispensable for embryonic stem cell self-renewal and mouse development. Mol Cell Biol , 23: 2699-2708 doi: 10.1128/MCB.23.8.2699-2708.2003
67
Wernig M, Meissner A, Cassady J P, Jaenisch R (2008). c-Myc is dispensable for direct reprogramming of mouse fibroblasts. Cell Stem Cell , 2: 10-12 doi: 10.1016/j.stem.2007.12.001
68
Wernig M, Meissner A, Foreman R, Brambrink T, Ku M, Hochedlinger K, Bernstein B E, Jaenisch R (2007). In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature , 448: 318-324 doi: 10.1038/nature05944
69
Wernig M, Zhao J P, Pruszak J, Hedlund E, Fu D, Soldner F, Broccoli V, Constantine-Paton M, Isacson O, Jaenisch R (2008). Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease. Proc Natl Acad Sci U S A , 105: 5856-5861 doi: 10.1073/pnas.0801677105
70
Wood H B, Episkopou V (1999). Comparative expression of the mouse Sox1, Sox2 and Sox3 genes from pre-gastrulation to early somite stages. Mech Dev , 86: 197-201 doi: 10.1016/S0925-4773(99)00116-1
71
Yu J, Vodyanik M A, Smuga-Otto K, Antosiewicz-Bourget J, Frane J L, Tian S, Nie J, Jonsdottir G A, Ruotti V, Stewart R, Slukvin I I, Thomson J A (2007). Induced pluripotent stem cell lines derived from human somatic cells. Science , 318: 1917-1920 doi: 10.1126/science.1151526
72
Zeineddine D, Papadimou E, Chebli K, Gineste M, Liu J, Grey C, Thurig S, Behfar A, Wallace V A, Skerjanc I S, Pucéat M (2006). Oct-3/4 dose dependently regulates specification of embryonic stem cells toward a cardiac lineage and early heart development. Dev Cell , 11: 535-546 doi: 10.1016/j.devcel.2006.07.013
