Chapter5 References Reference Abdollah, S., Macias-Silva, M., Tsukazaki, T., Hayashi, H., Attisano, L., and Wrana, J L (1997) TbetaRI phosphorylation of Smad2 on Ser465 and Ser467 is required for Smad2Smad4 complex formation and signaling J Biol Chem 272, 27678-27685 Ambrosetti, D C., Basilico, C., and Dailey, L (1997) Synergistic activation of the fibroblast growth factor enhancer by Sox2 and Oct-3 depends on protein-protein interactions facilitated by a specific spatial arrangement of factor binding sites Mol Cell Biol 17, 6321-6329 Attisano, L., Wrana, J L., Montalvo, E., and Massague, J (1996) Activation of signalling by the activin receptor complex Mol Cell Biol 16, 1066-1073 Aubert, J., Dunstan, H., Chambers, I., and Smith, A (2002) Functional gene screening in embryonic stem cells implicates Wnt antagonism in neural differentiation Nat Biotechnol 20, 1240-1245 Avilion, A A., Nicolis, S K., Pevny, L H., Perez, L., Vivian, N., and Lovell-Badge, R (2003) Multipotent cell lineages in early mouse development depend on SOX2 function Genes Dev 17, 126-140 Bakre, M M., Hoi, A., Mong, J C., Koh, Y Y., Wong, K Y., and Stanton, L W (2007) Generation of multipotential mesendodermal progenitors from mouse embryonic stem cells via sustained Wnt pathway activation J Biol Chem 282, 31703-31712 Beattie, G M., Lopez, A D., Bucay, N., Hinton, A., Firpo, M T., King, C C., and Hayek, A (2005) Activin A maintains pluripotency of human embryonic stem cells in the absence of feeder layers Stem Cells 23, 489-495 Besser, D (2004) Expression of nodal, lefty-a, and lefty-B in undifferentiated human embryonic stem cells requires activation of Smad2/3 J Biol Chem 279, 45076-45084 Bhattacharya, B., Miura, T., Brandenberger, R., Mejido, J., Luo, Y., Yang, A X., Joshi, B H., Ginis, I., Thies, R S., Amit, M., et al (2004) Gene expression in human embryonic stem cell lines: unique molecular signature Blood 103, 2956-2964 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., et al (2005) Core transcriptional regulatory circuitry in human embryonic stem cells Cell 122, 947-956 Brandenberger, R., Khrebtukova, I., Thies, R S., Miura, T., Jingli, C., Puri, R., Vasicek, T., Lebkowski, J., and Rao, M (2004) MPSS profiling of human embryonic stem cells BMC Dev Biol 4, 10 183 Brennan, J., Lu, C C., Norris, D P., Rodriguez, T A., Beddington, R S., and Robertson, E J (2001) Nodal signalling in the epiblast patterns the early mouse embryo Nature 411, 965-969 Brennan, J., Norris, D P., and Robertson, E J (2002) Nodal activity in the node governs left-right asymmetry Genes Dev 16, 2339-2344 Brons IG, Smithers LE, Trotter MW, Rugg-Gunn P, Sun B, Chuva de Sousa Lopes SM, Howlett SK, Clarkson A, Ahrlund-Richter L, Pedersen RA, Vallier L (2007), Derivation of pluripotent epiblast stem cells from mammalian embryos., Nature 448, 191-195 Brown, K A., Pietenpol, J A., and Moses, H L (2007) A tale of two proteins: differential roles and regulation of Smad2 and Smad3 in TGF-beta signaling J Cell Biochem 101, 9-33 Burns, C J., Persaud, S J., and Jones, P M (2006) Diabetes mellitus: a potential target for stem cell therapy Curr Stem Cell Res Ther 1, 255-266 Camus, A., Perea-Gomez, A., Moreau, A., and Collignon, J (2006) Absence of Nodal signaling promotes precocious neural differentiation in the mouse embryo Dev Biol 295, 743-755 Chambers, I., Colby, D., Robertson, M., Nichols, J., Lee, S., Tweedie, S., and Smith, A (2003) Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells Cell 113, 643-655 Chambers, I., and Smith, A (2004) Self-renewal of teratocarcinoma and embryonic stem cells Oncogene 23, 7150-7160 Chen, C., and Shen, M M (2004) Two modes by which Lefty proteins inhibit nodal signaling Curr Biol 14, 618-624 Chen, Y., and Schier, A F (2001) The zebrafish Nodal signal Squint functions as a morphogen Nature 411, 607-610 Chew, J L., Loh, Y H., Zhang, W., Chen, X., Tam, W L., Yeap, L S., Li, P., Ang, Y S., Lim, B., Robson, P., and Ng, H H (2005) Reciprocal transcriptional regulation of Pou5f1 and Sox2 via the Oct4/Sox2 complex in embryonic stem cells Mol Cell Biol 25, 6031-6046 Chu, J., Ding, J., Jeays-Ward, K., Price, S M., Placzek, M., and Shen, M M (2005) Non-cell-autonomous role for Cripto in axial midline formation during vertebrate embryogenesis Development 132, 5539-5551 Ciardiello, F., Dono, R., Kim, N., Persico, M G., and Salomon, D S (1991a) Expression of cripto, a novel gene of the epidermal growth factor gene family, leads to in 184 vitro transformation of a normal mouse mammary epithelial cell line Cancer Res 51, 1051-1054 Ciardiello, F., Kim, N., Saeki, T., Dono, R., Persico, M G., Plowman, G D., Garrigues, J., Radke, S., Todaro, G J., and Salomon, D S (1991b) Differential expression of epidermal growth factor-related proteins in human colorectal tumors Proc Natl Acad Sci U S A 88, 7792-7796 Conlon, F L., Lyons, K M., Takaesu, N., Barth, K S., Kispert, A., Herrmann, B., and Robertson, E J (1994) A primary requirement for nodal in the formation and maintenance of the primitive streak in the mouse Development 120, 1919-1928 Daheron, L., Opitz, S L., Zaehres, H., Lensch, W M., Andrews, P W., Itskovitz-Eldor, J., and Daley, G Q (2004) LIF/STAT3 signaling fails to maintain self-renewal of human embryonic stem cells Stem Cells 22, 770-778 Darr, H., Mayshar, Y., and Benvenisty, N (2006) Overexpression of NANOG in human ES cells enables feeder-free growth while inducing primitive ectoderm features Development 133, 1193-1201 Davila, J C., Cezar, G G., Thiede, M., Strom, S., Miki, T., and Trosko, J (2004) Use and application of stem cells in toxicology Toxicol Sci 79, 214-223 Di-Gregorio A, Sancho M, Stuckey DW, Crompton LA, Godwin J, Mishina Y, Rodriguez TA.(2007) BMP signalling inhibits premature neural differentiation in the mouse embryo Development 134, 3359-69 Dunn, N R., Vincent, S D., Oxburgh, L., Robertson, E J., and Bikoff, E K (2004) Combinatorial activities of Smad2 and Smad3 regulate mesoderm formation and patterning in the mouse embryo Development 131, 1717-1728 Dvash T, Sharon N, Yanuka O, Benvenisty N (2007), Molecular analysis of LEFTYexpressing cells in early human embryoid bodies, Stem Cells 25, 465-472 Fan, L., and Collodi, P (2006) Zebrafish embryonic stem cells Methods Enzymol 418, 64-77 Feldman, B., Gates, M A., Egan, E S., Dougan, S T., Rennebeck, G., Sirotkin, H I., Schier, A F., and Talbot, W S (1998) Zebrafish organizer development and germ-layer formation require nodal-related signals Nature 395, 181-185 Fukuda, H., and Takahashi, J (2005) Embryonic stem cells as a cell source for treating Parkinson's disease Expert Opin Biol Ther 5, 1273-1280 185 Funaba, M., Zimmerman, C M., and Mathews, L S (2002) Modulation of Smad2mediated signaling by extracellular signal-regulated kinase J Biol Chem 277, 4136141368 Gliniak, B C., McKenna, H J., Papayannopoulou, T., Thoma, B., and et al (1995) Targeted disruption of the low-affinity leukemia inhibitory factor receptor gene causes placental, skeletal, neural and metabolic defects and results in perinatal death Development 121, 1283-1299 Goldin, S N., and Papaioannou, V E (2003) Paracrine action of FGF4 during periimplantation development maintains trophectoderm and primitive endoderm Genesis 36, 40-47 Gu, Z., Nomura, M., Simpson, B B., Lei, H., Feijen, A., van den Eijnden-van Raaij, J., Donahoe, P K., and Li, E (1998) The type I activin receptor ActRIB is required for egg cylinder organization and gastrulation in the mouse Genes Dev 12, 844-857 Hamada, H., Meno, C., Watanabe, D., and Saijoh, Y (2002) Establishment of vertebrate left-right asymmetry Nat Rev Genet 3, 103-113 Hamatani, T., Carter, M G., Sharov, A A., and Ko, M S (2004) Dynamics of global gene expression changes during mouse preimplantation development Dev Cell 6, 117131 Harms, P W., and Chang, C (2003) Tomoregulin-1 (TMEFF1) inhibits nodal signaling through direct binding to the nodal coreceptor Cripto Genes Dev 17, 2624-2629 Hendrix, M J., Seftor, E A., Seftor, R E., Kasemeier-Kulesa, J., Kulesa, P M., and Postovit, L M (2007) Reprogramming metastatic tumour cells with embryonic microenvironments Nat Rev Cancer 7, 246-255 Hirano, T., Ishihara, K., and Hibi, M (2000) Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors Oncogene 19, 2548-2556 Ho, H Y., and Li, M (2006) Potential application of embryonic stem cells in Parkinson's disease: drug screening and cell therapy Regen Med 1, 175-182 Iannaccone, P M., Taborn, G U., Garton, R L., Caplice, M D., and Brenin, D R (1994) Pluripotent embryonic stem cells from the rat are capable of producing chimeras Dev Biol 163, 288-292 Inman, G J., Nicolas, F J., Callahan, J F., Harling, J D., Gaster, L M., Reith, A D., Laping, N J., and Hill, C S (2002) SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7 Mol Pharmacol 62, 65-74 186 James, D., Levine, A J., Besser, D., and Hemmati-Brivanlou, A (2005) TGFbeta/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells Development 132, 1273-1282 Jiang J, Chan YS, Loh YH, Cai J, Tong GQ, Lim CA, Robson P, Zhong S, Ng HH.(2008), A core Klf circuitry regulates self-renewal of embryonic stem cells, Nat Cell Biol 10, 353-360 Jinnin, M., Ihn, H., and Tamaki, K (2006) Characterization of SIS3, a novel specific inhibitor of Smad3, and its effect on transforming growth factor-beta1-induced extracellular matrix expression Mol Pharmacol 69, 597-607 Jornvall, H., Reissmann, E., Andersson, O., Mehrkash, M., and Ibanez, C F (2004) ALK7, a receptor for nodal, is dispensable for embryogenesis and left-right patterning in the mouse Mol Cell Biol 24, 9383-9389 Kitamura, R., Takahashi, T., Nakajima, N., Isodono, K., Asada, S., Ueno, H., Ueyama, T., Yoshikawa, T., Matsubara, H., and Oh, H (2007) Stage-specific role of endogenous Smad2 activation in cardiomyogenesis of embryonic stem cells Circ Res 101, 78-87 Larsson, J., Goumans, M J., Sjostrand, L J., van Rooijen, M A., Ward, D., Leveen, P., Xu, X., ten Dijke, P., Mummery, C L., and Karlsson, S (2001) Abnormal angiogenesis but intact hematopoietic potential in TGF-beta type I receptor-deficient mice Embo J 20, 1663-1673 Levine, A J., and Brivanlou, A H (2006) GDF3, a BMP inhibitor, regulates cell fate in stem cells and early embryos Development 133, 209-216 Li, J., Pan, G., Cui, K., Liu, Y., Xu, S., and Pei, D (2007) A dominant-negative form of mouse SOX2 induces trophectoderm differentiation and progressive polyploidy in mouse embryonic stem cells J Biol Chem 282, 19481-19492 Li, M., Sendtner, M., and Smith, A (1995) Essential function of LIF receptor in motor neurons Nature 378, 724-727 Li, Y., McClintick, J., Zhong, L., Edenberg, H J., Yoder, M C., and 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 Loh, Y H., Wu, Q., Chew, J L., Vega, V B., Zhang, W., Chen, X., Bourque, G., George, J., Leong, B., Liu, J., et al (2006) The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells Nat Genet 38, 431-440 Lowe, L A., Yamada, S., and Kuehn, M R (2001) Genetic dissection of nodal function in patterning the mouse embryo Development 128, 1831-1843 187 Lu, C C., and Robertson, E J (2004) Multiple roles for Nodal in the epiblast of the mouse embryo in the establishment of anterior-posterior patterning Dev Biol 273, 149159 Matin, M M., Walsh, J R., Gokhale, P J., Draper, J S., Bahrami, A R., Morton, I., Moore, H D., and Andrews, P W (2004) Specific knockdown of Oct4 and beta2microglobulin expression by RNA interference in human embryonic stem cells and embryonic carcinoma cells Stem Cells 22, 659-668 Matsuda, T., Nakamura, T., Nakao, K., Arai, T., Katsuki, M., Heike, T., and Yokota, T (1999) STAT3 activation is sufficient to maintain an undifferentiated state of mouse embryonic stem cells Embo J 18, 4261-4269 Mee, P J., O'Brien, C M., Thomson, H., van der Sar, S., Lakics, V., and Allsopp, T E (2006) Embryonic stem cells as a source of differentiated neural cells for pharmacological screens Methods Mol Biol 329, 353-369 Meno, C., Gritsman, K., Ohishi, S., Ohfuji, Y., Heckscher, E., Mochida, K., Shimono, A., Kondoh, H., Talbot, W S., Robertson, E J., et al (1999) Mouse Lefty2 and zebrafish antivin are feedback inhibitors of nodal signaling during vertebrate gastrulation Mol Cell 4, 287-298 Meno, C., Ito, Y., Saijoh, Y., Matsuda, Y., Tashiro, K., Kuhara, S., and Hamada, H (1997) Two closely-related left-right asymmetrically expressed genes, lefty-1 and lefty-2: their distinct expression domains, chromosomal linkage and direct neuralizing activity in Xenopus embryos Genes Cells 2, 513-524 Meno, C., Saijoh, Y., Fujii, H., Ikeda, M., Yokoyama, T., Yokoyama, M., Toyoda, Y., and Hamada, H (1996) Left-right asymmetric expression of the TGF beta-family member lefty in mouse embryos Nature 381, 151-155 Mitsui, K., Tokuzawa, Y., Itoh, H., Segawa, K., Murakami, M., Takahashi, K., Maruyama, M., Maeda, M., and Yamanaka, S (2003) The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells Cell 113, 631642 Moffat, J., and Sabatini, D M (2006) Building mammalian signalling pathways with RNAi screens Nat Rev Mol Cell Biol 7, 177-187 Molofsky, A V., Pardal, R., and Morrison, S J (2004) Diverse mechanisms regulate stem cell self-renewal Curr Opin Cell Biol 16, 700-707 Nakatake, Y., Fukui, N., Iwamatsu, Y., Masui, S., Takahashi, K., Yagi, R., Yagi, K., Miyazaki, J., Matoba, R., Ko, M S., and Niwa, H (2006) Klf4 cooperates with Oct3/4 188 and Sox2 to activate the Lefty1 core promoter in embryonic stem cells Mol Cell Biol 26, 7772-7782 Nichols, J., Chambers, I., Taga, T., and Smith, A (2001) Physiological rationale for responsiveness of mouse embryonic stem cells to gp130 cytokines Development 128, 2333-2339 Nichols, J., Zevnik, B., Anastassiadis, K., Niwa, H., Klewe-Nebenius, D., Chambers, I., Scholer, H., and Smith, A (1998) Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4 Cell 95, 379-391 Niwa, H., Burdon, T., Chambers, I., and Smith, A (1998) Self-renewal of pluripotent embryonic stem cells is mediated via activation of STAT3 Genes Dev 12, 2048-2060 Niwa, H., Miyazaki, J., and Smith, A G (2000) Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells Nat Genet 24, 372376 Nomura, M., and Li, E (1998) Smad2 role in mesoderm formation, left-right patterning and craniofacial development Nature 393, 786-790 Ogawa, K., Saito, A., Matsui, H., Suzuki, H., Ohtsuka, S., Shimosato, D., Morishita, Y., Watabe, T., Niwa, H., and Miyazono, K (2007) Activin-Nodal signaling is involved in propagation of mouse embryonic stem cells J Cell Sci 120, 55-65 Oh, S P., and Li, E (1997) The signaling pathway mediated by the type IIB activin receptor controls axial patterning and lateral asymmetry in the mouse Genes Dev 11, 1812-1826 Pease, S., and Williams, R L (1990) Formation of germ-line chimeras from embryonic stem cells maintained with recombinant leukemia inhibitory factor Exp Cell Res 190, 209-211 Pera, M F., Andrade, J., Houssami, S., Reubinoff, B., Trounson, A., Stanley, E G., Ward-van Oostwaard, D., and Mummery, C (2004) Regulation of human embryonic stem cell differentiation by BMP-2 and its antagonist noggin J Cell Sci 117, 1269-1280 Perea-Gomez, A., Vella, F D., Shawlot, W., Oulad-Abdelghani, M., Chazaud, C., Meno, C., Pfister, V., Chen, L., Robertson, E., Hamada, H., et al (2002) Nodal antagonists in the anterior visceral endoderm prevent the formation of multiple primitive streaks Dev Cell 3, 745-756 Pesce, M., and Scholer, H R (2001) Oct-4: gatekeeper in the beginnings of mammalian development Stem Cells 19, 271-278 Postovit, L M., Seftor, E A., Seftor, R E., and Hendrix, M J (2007) Targeting Nodal in malignant melanoma cells Expert Opin Ther Targets 11, 497-505 189 Pouton, C W., and Haynes, J M (2007) Embryonic stem cells as a source of models for drug discovery Nat Rev Drug Discov 6, 605-616 Rao, M (2004) Conserved and divergent paths that regulate self-renewal in mouse and human embryonic stem cells Dev Biol 275, 269-286 Raz, R., Lee, C K., Cannizzaro, L A., d'Eustachio, P., and Levy, D E (1999) Essential role of STAT3 for embryonic stem cell pluripotency Proc Natl Acad Sci U S A 96, 28462851 Reubinoff, B E., Pera, M F., Fong, C Y., Trounson, A., and Bongso, A (2000) Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro Nat Biotechnol 18, 399-404 Reynolds A, Leake D, Boese Q, Scaringe S, Marshall WS, Khvorova A (2004) Rational siRNA design for RNA interference Nat Biotechnol 22,326–330 Rodda, D J., Chew, J L., Lim, L H., Loh, Y H., Wang, B., Ng, H H., and Robson, P (2005) Transcriptional regulation of nanog by OCT4 and SOX2 J Biol Chem 280, 24731-24737 Rodriguez, R T., Velkey, J M., Lutzko, C., Seerke, R., Kohn, D B., O'Shea, K S., and Firpo, M T (2007) Manipulation of OCT4 levels in human embryonic stem cells results in induction of differential cell types Exp Biol Med (Maywood) 232, 1368-1380 Ross S, Cheung E, Petrakis TG, Howell M, Kraus WL, Hill CS (2006) Smads orchestrate specific histone modifications and chromatin remodeling to activate transcription EMBO J 4, 490-502 Saijoh, Y., Adachi, H., Mochida, K., Ohishi, S., Hirao, A., and Hamada, H (1999) Distinct transcriptional regulatory mechanisms underlie left-right asymmetric expression of lefty-1 and lefty-2 Genes Dev 13, 259-269 Saijoh, Y., Adachi, H., Sakuma, R., Yeo, C Y., Yashiro, K., Watanabe, M., Hashiguchi, H., Mochida, K., Ohishi, S., Kawabata, M., et al (2000) Left-right asymmetric expression of lefty2 and nodal is induced by a signaling pathway that includes the transcription factor FAST2 Mol Cell 5, 35-47 Sakuma, R., Ohnishi Yi, Y., Meno, C., Fujii, H., Juan, H., Takeuchi, J., Ogura, T., Li, E., Miyazono, K., and Hamada, H (2002) Inhibition of Nodal signalling by Lefty mediated through interaction with common receptors and efficient diffusion Genes Cells 7, 401412 Saloman, D S., Bianco, C., Ebert, A D., Khan, N I., De Santis, M., Normanno, N., Wechselberger, C., Seno, M., Williams, K., Sanicola, M., et al (2000) The EGF-CFC 190 family: novel epidermal growth factor-related proteins in development and cancer Endocr Relat Cancer 7, 199-226 Sampath, K., Rubinstein, A L., Cheng, A M., Liang, J O., Fekany, K., Solnica-Krezel, L., Korzh, V., Halpern, M E., and Wright, C V (1998) Induction of the zebrafish ventral brain and floorplate requires cyclops/nodal signalling Nature 395, 185-189 Sato, N., Meijer, L., Skaltsounis, L., Greengard, P., and Brivanlou, A H (2004) 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, 55-63 Schier, A F., and Shen, M M (2000) Nodal signalling in vertebrate development Nature 403, 385-389 Seiler, A E., Buesen, R., Visan, A., and Spielmann, H (2006) Use of murine embryonic stem cells in embryotoxicity assays: the embryonic stem cell test Methods Mol Biol 329, 371-395 Shen, M M (2007) Nodal signaling: developmental roles and regulation Development 134, 1023-1034 Shi, W., Wang, H., Pan, G., Geng, Y., Guo, Y., and Pei, D (2006) Regulation of the pluripotency marker Rex-1 by Nanog and Sox2 J Biol Chem 281, 23319-23325 Shiratori, H., Sakuma, R., Watanabe, M., Hashiguchi, H., Mochida, K., Sakai, Y., Nishino, J., Saijoh, Y., Whitman, M., and Hamada, H (2001) Two-step regulation of left-right asymmetric expression of Pitx2: initiation by nodal signaling and maintenance by Nkx2 Mol Cell 7, 137-149 Smith, A G., Heath, J K., Donaldson, D D., Wong, G G., Moreau, J., Stahl, M., and Rogers, D (1988) Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides Nature 336, 688-690 Smith, A G., and Hooper, M L (1987) Buffalo rat liver cells produce a diffusible activity which inhibits the differentiation of murine embryonal carcinoma and embryonic stem cells Dev Biol 121, 1-9 Smith JR, Vallier L, Lupo G, Alexander M, Harris WA, Pedersen RA (2008), Inhibition of Activin/Nodal signaling promotes specification of human embryonic stem cells into neuroectoderm, Dev Biol 313, 107-117 Stewart, C L., Kaspar, P., Brunet, L J., Bhatt, H., Gadi, I., Kontgen, F., and Abbondanzo, S J (1992) Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor Nature 359, 76-79 191 Tabibzadeh, S., and Hemmati-Brivanlou, A (2006) Lefty at the crossroads of "stemness" and differentiative events Stem Cells 24, 1998-2006 Takagi, Y., Takahashi, J., Saiki, H., Morizane, A., Hayashi, T., Kishi, Y., Fukuda, H., Okamoto, Y., Koyanagi, M., Ideguchi, M., et al (2005) Dopaminergic neurons generated from monkey embryonic stem cells function in a Parkinson primate model J Clin Invest 115, 102-109 Takahashi K, Yamanaka S (2006), Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors., Cell 126(4), 663-76 Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S.(2007), Induction of pluripotent stem cells from adult human fibroblasts by defined factors, Cell.131(5), 861-72 Takenaga, M., Fukumoto, M., and Hori, Y (2007) Regulated Nodal signaling promotes differentiation of the definitive endoderm and mesoderm from ES cells J Cell Sci 120, 2078-2090 Tesar, P J (2005) Derivation of germ-line-competent embryonic stem cell lines from preblastocyst mouse embryos Proc Natl Acad Sci U S A 102, 8239-8244 Tesar PJ, Chenoweth JG, Brook FA, Davies TJ, Evans EP, Mack DL, Gardner RL, McKay RD (2007), New cell lines from mouse epiblast share defining features with human embryonic stem cells, Nature 448, 196-199 Thomson, J A., Itskovitz-Eldor, J., Shapiro, S S., Waknitz, M A., Swiergiel, J J., Marshall, V S., and Jones, J M (1998) Embryonic stem cell lines derived from human blastocysts Science 282, 1145-1147 Thomson, J A., and Marshall, V S (1998) Primate embryonic stem cells Curr Top Dev Biol 38, 133-165 Topczewska, J M., Postovit, L M., Margaryan, N V., Sam, A., Hess, A R., Wheaton, W W., Nickoloff, B J., Topczewski, J., and Hendrix, M J (2006) Embryonic and tumorigenic pathways converge via Nodal signaling: role in melanoma aggressiveness Nat Med 12, 925-932 Ulloa, L., Creemers, J W., Roy, S., Liu, S., Mason, J., and Tabibzadeh, S (2001) Lefty proteins exhibit unique processing and activate the MAPK pathway J Biol Chem 276, 21387-21396 Ulloa, L., and Tabibzadeh, S (2001) Lefty inhibits receptor-regulated Smad phosphorylation induced by the activated transforming growth factor-beta receptor J Biol Chem 276, 21397-21404 192 Vackova, I., Ungrova, A., and Lopes, F (2007) Putative embryonic stem cell lines from pig embryos J Reprod Dev 53, 1137-1149 Vallier, L., Alexander, M., and Pedersen, R A (2005) Activin/Nodal and FGF pathways cooperate to maintain pluripotency of human embryonic stem cells J Cell Sci 118, 44954509 Vallier, L., Reynolds, D., and Pedersen, R A (2004) Nodal inhibits differentiation of human embryonic stem cells along the neuroectodermal default pathway Dev Biol 275, 403-421 Varga, A C., and Wrana, J L (2005) The disparate role of BMP in stem cell biology Oncogene 24, 5713-5721 Voss, A K., Thomas, T., and Gruss, P (1997) Germ line chimeras from female ES cells Exp Cell Res 230, 45-49 Wei, C L., Miura, T., Robson, P., Lim, S K., Xu, X Q., Lee, M Y., Gupta, S., Stanton, L., Luo, Y., Schmitt, J., et al (2005) Transcriptome profiling of human and murine ESCs identifies divergent paths required to maintain the stem cell state Stem Cells 23, 166-185 Wieduwilt Matthew J., (2003) SMAD3 in embryonic patterning, mesoderm induction and colorectal cancer induction in the mouse, University of Texas Southwestern Medical Center, phD dissertation Wolf, E., Kramer, R., Polejaeva, I., Thoenen, H., and Brem, G (1994) Efficient generation of chimaeric mice using embryonic stem cells after long-term culture in the presence of ciliary neurotrophic factor Transgenic Res 3, 152-158 Xiao, L., Yuan, X., and Sharkis, S J (2006) Activin A maintains self-renewal and regulates fibroblast growth factor, Wnt, and bone morphogenic protein pathways in human embryonic stem cells Stem Cells 24, 1476-1486 Xu, R H., Chen, X., Li, D S., Li, R., Addicks, G C., Glennon, C., Zwaka, T P., and Thomson, J A (2002) BMP4 initiates human embryonic stem cell differentiation to trophoblast Nat Biotechnol 20, 1261-1264 Xu, R H., Peck, R M., Li, D S., Feng, X., Ludwig, T., and Thomson, J A (2005) Basic FGF and suppression of BMP signaling sustain undifferentiated proliferation of human ES cells Nat Methods 2, 185-190 Yamamoto, H., Quinn, G., Asari, A., Yamanokuchi, H., Teratani, T., Terada, M., and Ochiya, T (2003) Differentiation of embryonic stem cells into hepatocytes: biological functions and therapeutic application Hepatology 37, 983-993 193 Yamamoto, M., Meno, C., Sakai, Y., Shiratori, H., Mochida, K., Ikawa, Y., Saijoh, Y., and Hamada, H (2001) The transcription factor FoxH1 (FAST) mediates Nodal signaling during anterior-posterior patterning and node formation in the mouse Genes Dev 15, 1242-1256 Yan, Y T., Gritsman, K., Ding, J., Burdine, R D., Corrales, J D., Price, S M., Talbot, W S., Schier, A F., and Shen, M M (1999) Conserved requirement for EGF-CFC genes in vertebrate left-right axis formation Genes Dev 13, 2527-2537 Yang, X., Li, C., Xu, X., and Deng, C (1998) The tumor suppressor SMAD4/DPC4 is essential for epiblast proliferation and mesoderm induction in mice Proc Natl Acad Sci U S A 95, 3667-3672 Ying, Q L., Nichols, J., Chambers, I., and Smith, A (2003) BMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3 Cell 115, 281-292 Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA (2007), Induced pluripotent stem cell lines derived from human somatic cells., Science 318, 1917-1920 Zeineddine, D., Papadimou, E., Chebli, K., Gineste, M., Liu, J., Grey, C., Thurig, S., Behfar, A., Wallace, V A., Skerjanc, I S., and Puceat, 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 Zhang, J., Tam, W L., Tong, G Q., Wu, Q., Chan, H Y., Soh, B S., Lou, Y., Yang, J., Ma, Y., Chai, L., et al (2006) Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1 Nat Cell Biol 8, 1114-1123 Zhang, J G., Owczarek, C M., Ward, L D., Howlett, G J., Fabri, L J., Roberts, B A., and Nicola, N A (1997) Evidence for the formation of a heterotrimeric complex of leukaemia inhibitory factor with its receptor subunits in solution Biochem J 325 ( Pt 3), 693-700 194 ... Bucay, N., Hinton, A., Firpo, M T., King, C C., and Hayek, A (20 05) Activin A maintains pluripotency of human embryonic stem cells in the absence of feeder layers Stem Cells 23, 489-4 95 Besser,... H., and Miyazono, K (2007) Activin-Nodal signaling is involved in propagation of mouse embryonic stem cells J Cell Sci 120, 55 - 65 Oh, S P., and Li, E (1997) The signaling pathway mediated by the. .. H D., and Andrews, P W (2004) Specific knockdown of Oct4 and beta2microglobulin expression by RNA interference in human embryonic stem cells and embryonic carcinoma cells Stem Cells 22, 659 -668