Pluripotency rush! Molecular cues for pluripotency, genetic reprogramming of adult stem cells, and widely multipotent adult cells

Pharmacology and Therapeutics

Volumn 124, Issue 1, 2009, Pages 23-30

  Beltrami, Antonio Paolo ^a   Cesselli, Daniela ^a   Beltrami, Carlo Alberto ^a  

^a UNIVERSITY OF UDINE   (Italy)

Author keywords

Adult stem cell; Embryonic stem cell; Induced pluripotent stem cell; Nanog; OCT4; Pluripotent stem cell; Sox2

Indexed keywords

ALKALINE PHOSPHATASE; BONE MORPHOGENETIC PROTEIN 4; BREAST CANCER RESISTANCE PROTEIN; CONNEXIN 43; FIBROBLAST GROWTH FACTOR 4; GLUCOSE TRANSPORTER 1; HIGH MOBILITY GROUP B2 PROTEIN; INTERLEUKIN 6; JANUS KINASE; KRUPPEL LIKE FACTOR 4; LEUKEMIA INHIBITORY FACTOR; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; MYC PROTEIN; NOGGIN; NOTCH RECEPTOR; OCTAMER TRANSCRIPTION FACTOR 4; OSTEOPONTIN; PHOSPHATIDYLINOSITOL 3 KINASE; POLYCOMB GROUP PROTEIN; SMAD2 PROTEIN; SMAD3 PROTEIN; SOMATOMEDIN C RECEPTOR; STAGE SPECIFIC EMBRYO ANTIGEN 4; STAT3 PROTEIN; THY 1 ANTIGEN; TRANSCRIPTION FACTOR NANOG; TRANSCRIPTION FACTOR SOX2; WNT PROTEIN;

ADULT STEM CELL; CELL DIFFERENTIATION; EMBRYONIC STEM CELL; EPIGENETICS; GENE CONTROL; GENE EXPRESSION; HUMAN; MULTIPOTENT STEM CELL; NEURAL STEM CELL; NONHUMAN; PHENOTYPE; PLURIPOTENT STEM CELL; PRIMORDIAL GERM CELL; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; STEM CELL TRANSPLANTATION; TISSUE REGENERATION;

ADULT STEM CELLS; ANIMALS; EPIGENESIS, GENETIC; HUMANS; MULTIPOTENT STEM CELLS; PLURIPOTENT STEM CELLS; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTORS;

EID: 68949157277     PISSN: 01637258     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.pharmthera.2009.06.003     Document Type: Review

References (131)

1. Aflatoonian B., and Moore H. Germ cells from mouse and human embryonic stem cells. Reproduction 132 5 (2006) 699-707
2. Anderson D.J., Gage F.H., and Weissman I.L. Can stem cells cross lineage boundaries?. Nat Med 7 4 (2001) 393-395
3. Anghileri E., Marconi S., Pignatelli A., Cifelli P., Galie M., Sbarbati A., Krampera M., Belluzzi O., and Bonetti B. Neuronal differentiation potential of human adipose-derived mesenchymal stem cells. Stem Cells Dev 17 5 (2008) 909-916
4. Armstrong L., Hughes O., Yung S., Hyslop L., Stewart R., Wappler I., Peters H., Walter T., Stojkovic P., Evans J., Stojkovic M., and Lako M. The role of PI3K/AKT, MAPK/ERK and NFkappabeta signalling in the maintenance of human embryonic stem cell pluripotency and viability highlighted by transcriptional profiling and functional analysis. Hum Mol Genet 15 11 (2006) 1894-1913
5. Babaie Y., Herwig R., Greber B., Brink T.C., Wruck W., Groth D., Lehrach H., Burdon T., and Adjaye J. Analysis of Oct4-dependent transcriptional networks regulating self-renewal and pluripotency in human embryonic stem cells. Stem Cells 25 2 (2007) 500-510
6. Beddington R.S., and Robertson E.J. An assessment of the developmental potential of embryonic stem cells in the midgestation mouse embryo. Development 105 4 (1989) 733-737
7. Beltrami A.P., Cesselli D., Bergamin N., Marcon P., Rigo S., Puppato E., D'Aurizio F., Verardo R., Piazza S., Pignatelli A., Poz A., Baccarani U., Damiani D., Fanin R., Mariuzzi L., Finato N., Masolini P., Burelli S., Belluzzi O., Schneider C., and Beltrami C.A. Multipotent cells can be generated in vitro from several adult human organs (heart, liver and bone marrow). Blood 110 9 (2007) 3438-3446
8. Ben-Porath I., Thomson M.W., Carey V.J., Ge R., Bell G.W., Regev A., and Weinberg R.A. An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet 40 5 (2008) 499-507
9. Ben-Shushan E., Sharir H., Pikarsky E., and Bergman Y. A dynamic balance between ARP-1/COUP-TFII, EAR-3/COUP-TFI, and retinoic acid receptor: Retinoid X receptor heterodimers regulates Oct-3/4 expression in embryonal carcinoma cells. Mol Cell Biol 15 2 (1995) 1034-1048
10. Bendall S.C., Stewart M.H., Menendez P., George D., Vijayaragavan K., Werbowetski-Ogilvie T., Ramos-Mejia V., Rouleau A., Yang J., Bosse M., Lajoie G., and Bhatia M. IGF and FGF cooperatively establish the regulatory stem cell niche of pluripotent human cells in vitro. Nature 448 7157 (2007) 1015-1021
11. Bernstein B.E., Mikkelsen T.S., Xie X., Kamal M., Huebert D.J., Cuff J., Fry B., Meissner A., Wernig M., Plath K., Jaenisch R., Wagschal A., Feil R., Schreiber S.L., and Lander E.S. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125 2 (2006) 315-326
12. Bianco P. Life in plastic is fantastic. Blood 110 9 (2007) 3090
13. Blau H.M., Brazelton T.R., and Weimann J.M. The evolving concept of a stem cell: Entity or function?. Cell 105 7 (2001) 829-841
14. Botquin V., Hess H., Fuhrmann G., Anastassiadis C., Gross M.K., Vriend G., and Scholer H.R. New POU dimer configuration mediates antagonistic control of an osteopontin preimplantation enhancer by Oct-4 and Sox-2. Genes Dev 12 13 (1998) 2073-2090
15. 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., and Young R.A. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122 6 (2005) 947-956
16. Boyer L.A., Plath K., Zeitlinger J., Brambrink T., Medeiros L.A., Lee T.I., Levine S.S., Wernig M., Tajonar A., Ray M.K., Bell G.W., Otte A.P., Vidal M., Gifford D.K., Young R.A., and Jaenisch R. Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 441 7091 (2006) 349-353
17. Brinster R.L., and Zimmermann J.W. Spermatogenesis following male germ-cell transplantation. Proc Natl Acad Sci U S A 91 24 (1994) 11298-11302
18. Burdon T., Stracey C., Chambers I., Nichols J., and Smith A. Suppression of SHP-2 and ERK signalling promotes self-renewal of mouse embryonic stem cells. Dev Biol 210 1 (1999) 30-43
19. Cao R., Tsukada Y., and Zhang Y. Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing. Mol Cell 20 6 (2005) 845-854
20. Cao R., and Zhang Y. The functions of E(Z)/EZH2-mediated methylation of lysine 27 in histone H3. Curr Opin Genet Dev 14 2 (2004) 155-164
21. Carter M.G., Sharov A.A., VanBuren V., Dudekula D.B., Carmack C.E., Nelson C., and Ko M.S. Transcript copy number estimation using a mouse whole-genome oligonucleotide microarray. Genome Biol 6 7 (2005) R61
22. Cartwright P., McLean C., Sheppard A., Rivett D., Jones K., and Dalton S. LIF/STAT3 controls ES cell self-renewal and pluripotency by a myc-dependent mechanism. Development 132 5 (2005) 885-896
23. Case J., Horvath T.L., Ballas C.B., March K.L., and Srour E.F. In vitro clonal analysis of murine pluripotent stem cells isolated from skeletal muscle and adipose stromal cells. Exp Hematol 36 2 (2008) 224-234
24. Cavalli G. Chromatin and epigenetics in development: Blending cellular memory with cell fate plasticity. Development 133 11 (2006) 2089-2094
25. Cerny J., and Quesenberry P.J. Chromatin remodeling and stem cell theory of relativity. J Cell Physiol 201 1 (2004) 1-16
26. Cesselli D., Beltrami A.P., Rigo S., Bergamin N., D'Aurizio F., Verardo R., Piazza S., Klaric E., Fanin R., Toffoletto B., Marzinotto S., Mariuzzi L., Finato N., Pandolfi M., Leri A., Schneider C., Beltrami C.A., and Anversa P. Multipotent progenitor cells are present in human peripheral blood. Circ Res 104 10 (2009) 1225-1234
27. Chambers I., Colby D., Robertson M., Nichols J., Lee S., Tweedie S., and Smith A. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell 113 5 (2003) 643-655
28. Chien K.R. Regenerative medicine and human models of human disease. Nature 453 7193 (2008) 302-305
29. Conrad S., Renninger M., Hennenlotter J., Wiesner T., Just L., Bonin M., Aicher W., Buhring H.J., Mattheus U., Mack A., Wagner H.J., Minger S., Matzkies M., Reppel M., Hescheler J., Sievert K.D., Stenzl A., and Skutella T. Generation of pluripotent stem cells from adult human testis. Nature 456 7220 (2008) 344-349
30. Cowan C.A., Atienza J., Melton D.A., and Eggan K. Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells. Science 309 5739 (2005) 1369-1373
31. D'Aurizio F., Marcon P., Bergamin N., Martini S., Puppato E., Toffoletto B., Finato N., Livi U., Poz A., Cesselli D., Beltrami A.P., and Beltrami C.A. Dynamic evaluation of cardiac stem cell (CSC) outgrowth from human primary explants [Late-Breaking Basic Science Abstract]. Circ Res 101 11 (2007) 1210
32. D'Ippolito G., Diabira S., Howard G.A., Menei P., Roos B.A., and Schiller P.C. Marrow-isolated adult multilineage inducible (MIAMI) cells, a unique population of postnatal young and old human cells with extensive expansion and differentiation potential. J Cell Sci 117 Pt 14 (2004) 2971-2981
33. D'Ippolito G., Howard G.A., Roos B.A., and Schiller P.C. Isolation and characterization of marrow-isolated adult multilineage inducible (MIAMI) cells. Exp Hematol 34 11 (2006) 1608-1610
34. Do J.T., and Scholer H.R. Nuclei of embryonic stem cells reprogram somatic cells. Stem Cells 22 6 (2004) 941-949
35. Dravid G., Ye Z., Hammond H., Chen G., Pyle A., Donovan P., Yu X., and Cheng L. Defining the role of Wnt/beta-catenin signaling in the survival, proliferation, and self-renewal of human embryonic stem cells. Stem Cells 23 10 (2005) 1489-1501
36. Dvorak P., Dvorakova D., Koskova S., Vodinska M., Najvirtova M., Krekac D., and Hampl A. Expression and potential role of fibroblast growth factor 2 and its receptors in human embryonic stem cells. Stem Cells 23 8 (2005) 1200-1211
37. Fazzio T.G., Huff J.T., and Panning B. An RNAi screen of chromatin proteins identifies Tip60-p400 as a regulator of embryonic stem cell identity. Cell 134 1 (2008) 162-174
38. Fernandes K.J., McKenzie I.A., Mill P., Smith K.M., Akhavan M., Barnabe-Heider F., Biernaskie J., Junek A., Kobayashi N.R., Toma J.G., Kaplan D.R., Labosky P.A., Rafuse V., Hui C.C., and Miller F.D. A dermal niche for multipotent adult skin-derived precursor cells. Nat Cell Biol 6 11 (2004) 1082-1093
39. Fuhrmann G., Chung A.C., Jackson K.J., Hummelke G., Baniahmad A., Sutter J., Sylvester I., Scholer H.R., and Cooney A.J. Mouse germline restriction of Oct4 expression by germ cell nuclear factor. Dev Cell 1 3 (2001) 377-387
40. Gimble J.M., Katz A.J., and Bunnell B.A. Adipose-derived stem cells for regenerative medicine. Circ Res 100 9 (2007) 1249-1260
41. Ginis I., Luo Y., Miura T., Thies S., Brandenberger R., Gerecht-Nir S., Amit M., Hoke A., Carpenter M.K., Itskovitz-Eldor J., and Rao M.S. Differences between human and mouse embryonic stem cells. Dev Biol 269 2 (2004) 360-380
42. Guan K., Nayernia K., Maier L.S., Wagner S., Dressel R., Lee J.H., Nolte J., Wolf F., Li M., Engel W., and Hasenfuss G. Pluripotency of spermatogonial stem cells from adult mouse testis. Nature 440 7088 (2006) 1199-1203
43. Hao J., Li T.G., Qi X., Zhao D.F., and Zhao G.Q. WNT/beta-catenin pathway up-regulates Stat3 and converges on LIF to prevent differentiation of mouse embryonic stem cells. Dev Biol 290 1 (2006) 81-91
44. He S., Pant D., Schiffmacher A., Meece A., and Keefer C.L. Lymphoid enhancer factor 1-mediated Wnt signaling promotes the initiation of trophoblast lineage differentiation in mouse embryonic stem cells. Stem Cells 26 4 (2008) 842-849
45. Hochedlinger K., Yamada Y., Beard C., and Jaenisch R. Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues. Cell 121 3 (2005) 465-477
46. Humphrey R.K., Beattie G.M., Lopez A.D., Bucay N., King C.C., Firpo M.T., Rose-John S., and Hayek A. Maintenance of pluripotency in human embryonic stem cells is STAT3 independent. Stem Cells 22 4 (2004) 522-530
47. Hyslop L., Stojkovic M., Armstrong L., Walter T., Stojkovic P., Przyborski S., Herbert M., Murdoch A., Strachan T., and Lako M. Downregulation of Nanog induces differentiation of human embryonic stem cells to extraembryonic lineages. Stem Cells 23 8 (2005) 1035-1043
48. ISCI. Characterization of human embryonic stem cell lines by the International Stem Cell Initiative. Nat Biotechnol 25 7 (2007) 803-816
49. James D., Levine A.J., Besser D., and Hemmati-Brivanlou A. TGFbeta/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells. Development 132 6 (2005) 1273-1282
50. Jiang J., Chan Y.S., Loh Y.H., Cai J., Tong G.Q., Lim C.A., Robson P., Zhong S., and Ng H.H. A core Klf circuitry regulates self-renewal of embryonic stem cells. Nat Cell Biol 10 3 (2008) 353-360
51. Jiang Y., Jahagirdar B.N., Reinhardt R.L., Schwartz R.E., Keene C.D., Ortiz-Gonzalez X.R., Reyes M., Lenvik T., Lund T., Blackstad M., Du J., Aldrich S., Lisberg A., Low W.C., Largaespada D.A., and Verfaillie C.M. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418 6893 (2002) 41-49
52. Kaji K., Caballero I.M., MacLeod R., Nichols J., Wilson V.A., and Hendrich B. The NuRD component Mbd3 is required for pluripotency of embryonic stem cells. Nat Cell Biol 8 3 (2006) 285-292
53. Kaji K., Norrby K., Paca A., Mileikovsky M., Mohseni P., and Woltjen K. Virus-free induction of pluripotency and subsequent excision of reprogramming factors. Nature 458 7239 (2009) 771-775
54. Keenen B., and de la Serna I.L. Chromatin remodeling in embryonic stem cells: Regulating the balance between pluripotency and differentiation. J Cell Physiol 219 1 (2009) 1-7
55. Kern S., Eichler H., Stoeve J., Kluter H., and Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 24 5 (2006) 1294-1301
56. Kim J., Chu J., Shen X., Wang J., and Orkin S.H. An extended transcriptional network for pluripotency of embryonic stem cells. Cell 132 6 (2008) 1049-1061
57. Kim J.B., Sebastiano V., Wu G., Arauzo-Bravo M.J., Sasse P., Gentile L., Ko K., Ruau D., Ehrich M., van den Boom D., Meyer J., Hubner K., Bernemann C., Ortmeier C., Zenke M., Fleischmann B.K., Zaehres H., and Scholer H.R. Oct4-induced pluripotency in adult neural stem cells. Cell 136 3 (2009) 411-419
58. Kirkland M.A. A phase space model of hemopoiesis and the concept of stem cell renewal. Exp Hematol 32 6 (2004) 511-519
59. Kubota H., Avarbock M.R., and Brinster R.L. Spermatogonial stem cells share some, but not all, phenotypic and functional characteristics with other stem cells. Proc Natl Acad Sci U S A 100 11 (2003) 6487-6492
60. Kubota H., Avarbock M.R., and Brinster R.L. Growth factors essential for self-renewal and expansion of mouse spermatogonial stem cells. Proc Natl Acad Sci U S A 101 47 (2004) 16489-16494
61. Kubota H., and Brinster R.L. Culture of rodent spermatogonial stem cells, male germline stem cells of the postnatal animal. Methods Cell Biol 86 (2008) 59-84
62. Kucia M., Halasa M., Wysoczynski M., Baskiewicz-Masiuk M., Moldenhawer S., Zuba-Surma E., Czajka R., Wojakowski W., Machalinski B., and Ratajczak M.Z. Morphological and molecular characterization of novel population of CXCR4+ SSEA-4+ Oct-4+ very small embryonic-like cells purified from human cord blood: Preliminary report. Leukemia 21 2 (2007) 297-303
63. Kucia M., Reca R., Campbell F.R., Zuba-Surma E., Majka M., Ratajczak J., and Ratajczak M.Z. A population of very small embryonic-like (VSEL) CXCR4(+)SSEA-1(+)Oct-4(+) stem cells identified in adult bone marrow. Leukemia 20 5 (2006) 857-869
64. Lee M.G., Villa R., Trojer P., Norman J., Yan K.P., Reinberg D., Di Croce L., and Shiekhattar R. Demethylation of H3K27 regulates polycomb recruitment and H2A ubiquitination. Science 318 5849 (2007) 447-450
65. Lengner C.J., Camargo F.D., Hochedlinger K., Welstead G.G., Zaidi S., Gokhale S., Scholer H.R., Tomilin A., and Jaenisch R. Oct4 expression is not required for mouse somatic stem cell self-renewal. Cell Stem Cell 1 4 (2007) 403-415
66. Lengner C.J., Welstead G.G., and Jaenisch R. The pluripotency regulator Oct4: A role in somatic stem cells?. Cell Cycle 7 6 (2008) 725-728
67. Lensch M.W., Daheron L., and Schlaeger T.M. Pluripotent stem cells and their niches. Stem Cell Rev 2 3 (2006) 185-201
68. Lensch M.W., Schlaeger T.M., Zon L.I., and Daley G.Q. Teratoma formation assays with human embryonic stem cells: A rationale for one type of human-animal chimera. Cell Stem Cell 1 3 (2007) 253-258
69. Levasseur D.N., Wang J., Dorschner M.O., Stamatoyannopoulos J.A., and Orkin S.H. Oct4 dependence of chromatin structure within the extended Nanog locus in ES cells. Genes Dev 22 5 (2008) 575-580
70. Li J., Pan G., Cui K., Liu Y., Xu S., and Pei D. A dominant-negative form of mouse Sox2 induces trophectoderm differentiation and progressive polyploidy in mouse embryonic stem cells. J Biol Chem 282 27 (2007) 19481-19492
71. Lin G., Garcia M., Ning H., Banie L., Guo Y.L., Lue T.F., and Lin C.S. Defining stem and progenitor cells within adipose tissue. Stem Cells Dev 17 6 (2008) 1053-1063
72. Loh Y.H., Wu Q., Chew J.L., Vega V.B., Zhang W., Chen X., Bourque G., George J., Leong B., Liu J., Wong K.Y., Sung K.W., Lee C.W., Zhao X.D., Chiu K.P., Lipovich L., Kuznetsov V.A., Robson P., Stanton L.W., Wei C.L., Ruan Y., Lim B., and Ng H.H. The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat Genet 38 4 (2006) 431-440
73. Loh Y.H., Zhang W., Chen X., George J., and Ng H.H. Jmjd1a and Jmjd2c histone H3 Lys 9 demethylases regulate self-renewal in embryonic stem cells. Genes Dev 21 20 (2007) 2545-2557
74. Lowell S., Benchoua A., Heavey B., and Smith A.G. Notch promotes neural lineage entry by pluripotent embryonic stem cells. PLoS Biol 4 5 (2006) e121
75. Ludwig T.E., Bergendahl V., Levenstein M.E., Yu J., Probasco M.D., and Thomson J.A. Feeder-independent culture of human embryonic stem cells. Nat Methods 3 8 (2006) 637-646
76. Maherali N., Ahfeldt T., Rigamonti A., Utikal J., Cowan C., and Hochedlinger K. A high-efficiency system for the generation and study of human induced pluripotent stem cells. Cell Stem Cell 3 3 (2008) 340-345
77. Mayshar Y., Rom E., Chumakov I., Kronman A., Yayon A., and Benvenisty N. Fibroblast growth factor 4 and its novel splice isoform have opposing effects on the maintenance of human embryonic stem cell self-renewal. Stem Cells 26 3 (2008) 767-774
78. Meissner A., Wernig M., and Jaenisch R. Direct reprogramming of genetically unmodified fibroblasts into pluripotent stem cells. Nat Biotechnol 25 10 (2007) 1177-1181
79. Meshorer E., and Misteli T. Chromatin in pluripotent embryonic stem cells and differentiation. Nat Rev Mol Cell Biol 7 7 (2006) 540-546
80. Meshorer E., Yellajoshula D., George E., Scambler P.J., Brown D.T., and Misteli T. Hyperdynamic plasticity of chromatin proteins in pluripotent embryonic stem cells. Dev Cell 10 1 (2006) 105-116
81. Mitsui K., Tokuzawa Y., Itoh H., Segawa K., Murakami M., Takahashi K., Maruyama M., Maeda M., and Yamanaka S. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell 113 5 (2003) 631-642
82. Miyagi S., Nishimoto M., Saito T., Ninomiya M., Sawamoto K., Okano H., Muramatsu M., Oguro H., Iwama A., and Okuda A. The Sox2 regulatory region 2 functions as a neural stem cell-specific enhancer in the telencephalon. J Biol Chem 281 19 (2006) 13374-13381
83. Nagy A., Gocza E., Diaz E.M., Prideaux V.R., Ivanyi E., Markkula M., and Rossant J. Embryonic stem cells alone are able to support fetal development in the mouse. Development 110 3 (1990) 815-821
84. Nakatake Y., Fukui N., Iwamatsu Y., Masui S., Takahashi K., Yagi R., Yagi K., Miyazaki J., Matoba R., Ko M.S., and Niwa H. Klf4 cooperates with Oct3/4 and Sox2 to activate the Lefty1 core promoter in embryonic stem cells. Mol Cell Biol 26 20 (2006) 7772-7782
85. Nichols J., Zevnik B., Anastassiadis K., Niwa H., Klewe-Nebenius D., Chambers I., Scholer H., and Smith A. Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell 95 3 (1998) 379-391
86. Niwa H. How is pluripotency determined and maintained?. Development 134 4 (2007) 635-646
87. Niwa H., Miyazaki J., and Smith A.G. Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat Genet 24 4 (2000) 372-376
88. Noggle S.A., Weiler D., and Condie B.G. Notch signaling is inactive but inducible in human embryonic stem cells. Stem Cells 24 7 (2006) 1646-1653
89. O'Carroll D., Erhardt S., Pagani M., Barton S.C., Surani M.A., and Jenuwein T. The polycomb-group gene Ezh2 is required for early mouse development. Mol Cell Biol 21 13 (2001) 4330-4336
90. Okita K., Ichisaka T., and Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature 448 7151 (2007) 313-317
91. Okita K., Nakagawa M., Hyenjong H., Ichisaka T., and Yamanaka S. Generation of mouse induced pluripotent stem cells without viral vectors. Science 322 5903 (2008) 949-953
92. Paling N.R., Wheadon H., Bone H.K., and Welham M.J. Regulation of embryonic stem cell self-renewal by phosphoinositide 3-kinase-dependent signaling. J Biol Chem 279 46 (2004) 48063-48070
93. Palmqvist L., Glover C.H., Hsu L., Lu M., Bossen B., Piret J.M., Humphries R.K., and Helgason C.D. Correlation of murine embryonic stem cell gene expression profiles with functional measures of pluripotency. Stem Cells 23 5 (2005) 663-680
94. Pan G., and Thomson J.A. Nanog and transcriptional networks in embryonic stem cell pluripotency. Cell Res 17 1 (2007) 42-49
95. Pasini D., Bracken A.P., Hansen J.B., Capillo M., and Helin K. The polycomb group protein Suz12 is required for embryonic stem cell differentiation. Mol Cell Biol 27 10 (2007) 3769-3779
96. Pasini D., Hansen K.H., Christensen J., Agger K., Cloos P.A., and Helin K. Coordinated regulation of transcriptional repression by the RBP2 H3K4 demethylase and polycomb-repressive complex 2. Genes Dev 22 10 (2008) 1345-1355
97. Pyle A.D., Lock L.F., and Donovan P.J. Neurotrophins mediate human embryonic stem cell survival. Nat Biotechnol 24 3 (2006) 344-350
98. Qi X., Li T.G., Hao J., Hu J., Wang J., Simmons H., Miura S., Mishina Y., and Zhao G.Q. BMP4 supports self-renewal of embryonic stem cells by inhibiting mitogen-activated protein kinase pathways. Proc Natl Acad Sci U S A 101 16 (2004) 6027-6032
99. Randall T.D., and Weissman I.L. Characterization of a population of cells in the bone marrow that phenotypically mimics hematopoietic stem cells: Resting stem cells or mystery population?. Stem Cells 16 1 (1998) 38-48
100. Ratajczak M.Z., Zuba-Surma E.K., Shin D.M., Ratajczak J., and Kucia M. Very small embryonic-like (VSEL) stem cells in adult organs and their potential role in rejuvenation of tissues and longevity. Exp Gerontol 43 11 (2008) 1009-1017
101. Richards M., Tan S.P., Tan J.H., Chan W.K., and Bongso A. The transcriptome profile of human embryonic stem cells as defined by SAGE. Stem Cells 22 1 (2004) 51-64
102. Rodda D.J., Chew J.L., Lim L.H., Loh Y.H., Wang B., Ng H.H., and Robson P. Transcriptional regulation of nanog by OCT4 and Sox2. J Biol Chem 280 26 (2005) 24731-24737
103. Sato N., Meijer L., Skaltsounis L., Greengard P., and Brivanlou A.H. Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor. Nat Med 10 1 (2004) 55-63
104. Sekkai D., Gruel G., Herry M., Moucadel V., Constantinescu S.N., Albagli O., Tronik-Le Roux D., Vainchenker W., and Bennaceur-Griscelli A. Microarray analysis of LIF/Stat3 transcriptional targets in embryonic stem cells. Stem Cells 23 10 (2005) 1634-1642
105. Seo M.J., Suh S.Y., Bae Y.C., and Jung J.S. Differentiation of human adipose stromal cells into hepatic lineage in vitro and in vivo. Biochem Biophys Res Commun 328 1 (2005) 258-264
106. Slack J.M. Origin of stem cells in organogenesis. Science 322 5907 (2008) 1498-1501
107. Smith A. A glossary for stem cell biology. Nature 441 4954 (2006) 1060
108. Smith A.G., Heath J.K., Donaldson D.D., Wong G.G., Moreau J., Stahl M., and Rogers D. Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides. Nature 336 6200 (1988) 688-690
109. Stewart M.H., Bendall S.C., and Bhatia M. Deconstructing human embryonic stem cell cultures: Niche regulation of self-renewal and pluripotency. J Mol Med 86 8 (2008) 875-886
110. Szutorisz H., Canzonetta C., Georgiou A., Chow C.M., Tora L., and Dillon N. Formation of an active tissue-specific chromatin domain initiated by epigenetic marking at the embryonic stem cell stage. Mol Cell Biol 25 5 (2005) 1804-1820
111. Szutorisz H., and Dillon N. The epigenetic basis for embryonic stem cell pluripotency. Bioessays 27 12 (2005) 1286-1293
112. Takahashi K., Murakami M., and Yamanaka S. Role of the phosphoinositide 3-kinase pathway in mouse embryonic stem (ES) cells. Biochem Soc Trans 33 Pt 6 (2005) 1522-1525
113. Takahashi K., and Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126 4 (2006) 663-676
114. Takeuchi T., Watanabe Y., Takano-Shimizu T., and Kondo S. Roles of jumonji and jumonji family genes in chromatin regulation and development. Dev Dyn 235 9 (2006) 2449-2459
115. Vallier L., Alexander M., and Pedersen R.A. Activin/nodal and FGF pathways cooperate to maintain pluripotency of human embryonic stem cells. J Cell Sci 118 Pt 19 (2005) 4495-4509
116. Wagers A.J., and Weissman I.L. Plasticity of adult stem cells. Cell 116 5 (2004) 639-648
117. Walsh J., and Andrews P.W. Expression of Wnt and Notch pathway genes in a pluripotent human embryonal carcinoma cell line and embryonic stem cell. Apmis 111 1 (2003) 197-210 discussion 210-191
118. Wang Q.T., Piotrowska K., Ciemerych M.A., Milenkovic L., Scott M.P., Davis R.W., and Zernicka-Goetz M. A genome-wide study of gene activity reveals developmental signaling pathways in the preimplantation mouse embryo. Dev Cell 6 1 (2004) 133-144
119. Wang J., Rao S., Chu J., Shen X., Levasseur D.N., Theunissen T.W., and Orkin S.H. A protein interaction network for pluripotency of embryonic stem cells. Nature 444 7117 (2006) 364-368
120. Wang G., Zhang H., Zhao Y., Li J., Cai J., Wang P., Meng S., Feng J., Miao C., Ding M., Li D., and Deng H. Noggin and bFGF cooperate to maintain the pluripotency of human embryonic stem cells in the absence of feeder layers. Biochem Biophys Res Commun 330 3 (2005) 934-942
121. Wernig M., Meissner A., Foreman R., Brambrink T., Ku M., Hochedlinger K., Bernstein B.E., and Jaenisch R. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 448 7151 (2007) 318-324
122. Williams R.R., Azuara V., Perry P., Sauer S., Dvorkina M., Jorgensen H., Roix J., McQueen P., Misteli T., Merkenschlager M., and Fisher A.G. Neural induction promotes large-scale chromatin reorganisation of the Mash1 locus. J Cell Sci 119 Pt 1 (2006) 132-140
123. Wurmser A.E., and Gage F.H. Stem cells: Cell fusion causes confusion. Nature 416 6880 (2002) 485-487
124. Xu R.H., Peck R.M., Li D.S., Feng X., Ludwig T., and Thomson J.A. Basic FGF and suppression of BMP signaling sustain undifferentiated proliferation of human ES cells. Nat Methods 2 3 (2005) 185-190
125. Xu Y., Shi Y., and Ding S. A chemical approach to stem-cell biology and regenerative medicine. Nature 453 7193 (2008) 338-344
126. Ying Q.L., Nichols J., Chambers I., and Smith A. BMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3. Cell 115 3 (2003) 281-292
127. Ying Q.L., Nichols J., Evans E.P., and Smith A.G. Changing potency by spontaneous fusion. Nature 416 6880 (2002) 545-548
128. Yu J., and Thomson J.A. Pluripotent stem cell lines. Genes Dev 22 15 (2008) 1987-1997
129. Zangrossi S., Marabese M., Broggini M., Giordano R., D'Erasmo M., Montelatici E., Intini D., Neri A., Pesce M., Rebulla P., and Lazzari L. Oct-4 expression in adult human differentiated cells challenges its role as a pure stem cell marker. Stem Cells 25 7 (2007) 1675-1680
130. Zipori D. The nature of stem cells: State rather than entity. Nat Rev Genet 5 11 (2004) 873-878
131. Zipori D. The stem state: Plasticity is essential, whereas self-renewal and hierarchy are optional. Stem Cells 23 6 (2005) 719-726