Abstract
Neurons and glia are important targets of human embryonic stem cell research promising a renewable source of these differentiated cells for biomedical research and regenerative medicine. Neurons and glia are derived, in vivo from the neuroepithelium of the neural tube. Concomitant to development along the anterior to posterior axis, gradients of morphogens across the dorsal and ventral axis of the neural tube establish positional codes that generate distinct progenitor domains and ultimately specify subtype identity. The neural rosette is the developmental signature of neuroprogenitors in cultures of differentiating embryonic stem cells; rosettes are radial arrangements of columnar cells that express many of the proteins expressed in neuroepithelial cells in the neural tube. In addition to similar morphology, neuroprogenitors within neural rosettes differentiate into the main classes of progeny of neuroepithelial cells in vivo: neurons, oligodendrocytes, and astrocytes. Despite these similarities, important differences exist and the extent to which neural rosettes can model neurogenesis in vivo is not yet clear. Here, the authors review the recent studies on the development and differentiation of neural rosettes from human embryonic stem cells. The authors focus on efforts to generate motor neurons and oligodendrocytes in vitro as representative of the challenges to obtaining the progeny of a single progenitor domain with in vitro methods. Opportunities for further progress are discussed.
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Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. Scence 1998; 282:1145–1147.
Ji RR, Stichartz G. Sci STEK 2004;2004:reE14.
Miller G. Science 2005;308:778–781.
Reubinoff BE, Pera MF, Fong CY, Trounson A, Bongso A. Nat Biotechnol 2000;18:399–404.
Reubinoff BE, Itsykson P, Turetsky T, et al. Nat Biotechnol 2001; 19:1134–1140.
Carpenter MK, Inokuma MS, Denham J, Mujtaba T, Chiu CP, Rao MS. Exp Neurol 2001;172:383–397.
Itskovitz-Eldor J, Schuldiner M, Karsenti D, et al. Mol Med 2000; 6:88–95.
Schuldiner M, Yanuka O, Itskovitz-Eldor J, Melton DA, Benvenisty N. Proc Natl Acad Sci USA 2000;97:11,307–11,312.
Pera MF, Trounson AC. Development 2004;131:5515–5525.
Attisano L, Wrana JL. Science 2000;296:1646, 1647.
Moreau M, Leclerc C. Int J Dev Biol 2004;48:75–84.
Muñoz-Sanjuán I, Brivanlou AH. Nat Rev Neurosci 2002;3.
Dupont S, Zacchigan L, Cordenonsi M, et al. Cell 2005;121:87–99.
Wilson SI, Graziano E, Harland R, Jessell TM, Edlund T. Curr Biol 2000;10:421–429.
Wilson SI, Rydstrom A, Trimborn T, et al. Nature 2001;1411: 325–330.
Sasai Y. Nature 2005;435:433, 434.
Detraitt ER, George TM, Etchevers HC, Gilbert JR, Vekemans M, Speer MC. Neurotoxicol Teratol 2005;27:515–524.
Gotz M, Barde YA. Neuron 2005;46:369–372.
Mori T, Buffo A, Gotz M. Curr Top Dev Biol 2005;69:65–97.
Fujita S. J Comp Neurol 1964;122.
Sauer FC. J Comp Neurol 1935;62.
Ever L, Gaiano N. Curr Opin Neurobiol 2005;15:29–33.
Rakic P. Glia 2003;43:19–32.
Hatakeyama J, Bessho Y, Katoh K, et al. Development 2004;131:5539–5550.
Glaser T, Brustle O. Trends Neurosci 2005;28:397–400.
Le Douarin NM, Creuzet S, Couly G, Dypin E. Development 2004;131:4637–4650.
Le Douarin NM, Dupin E. Curr Opin Genet Dev 2003;13:529–536.
Grundy D, Schemann M. Curr Opin Gastroenterol 2005;21:176–182.
Anderson DJ. Philos Trans R Soc Lond B Biol Sci 2000;355:953–964.
Kawasaki H, Mizuseki K, Nishikawa S, et al. Neuron 2000;28:31–40.
Mizuseki K, Sakamoto T, Watanabe K, et al. Proc Natl Acad Sci USA 2003;100:5828–5833.
Pomp O, Brokhman I, Ben-Dor I, Reubinoff B, Goldstein RS. Stem Cell 2005;23:923–930.
Briscoe J, Ericson J. Curr Opi Neurobiol 2001;11:43–49.
Helms AW, Johnson JE. Curr Opin Neurobiol 2003;13:42–49.
Jessell TM. Nat Rev Genet 2000;1:20–29.
Guthrie S. Curr Biol 2002;12:R488-R490.
Guthrie S. Curr Biol 2004;14:R166-R168.
Caspary T, Anderson KV. Nat Rev Neurosci;2003;4:289–297.
Price SR, Briscoe J. Mech Dev 2004;121:1103–1115.
Chizhikov VV, Millen KJ. Dev Biol 2005;277:287–295.
Wilson L, Maden M. Dev Biol 2005;282:1–13.
Zhang J, Li L. Dev Biol 2005;284:1–11.
Jacob J, Briscoe J. EMBO Rep 2003;4:761–765.
Ericson J, Briscoe J, Rashbass P, van Heyningen V, Jessell TM. Cold Spring Harb Symp Quant Biol 1997;62:451–466.
Stamataki D, Ulloa F, Tsoni SV, Mynett A, Briscoe J. Genes Dev 2005;19:626–641.
Appel B, Eisen JS. Neuron 2003;40:461–464.
Novitch BG, Wichterle H, Jessell TM, Sockanathan S. Neuron 2003;40:8–195.
Wegner M, Stolt CC. Trends Neurosci 2005;28:583–588.
Episkopou V. Trends Neurosci 2005;28:219–221.
Graham V, Khudyakov J, Ellis P, Pevny L. Neuron 2003;39: 749–765.
Pevny LH, Lovell-Badge R. Curr Opin Genet Dev 1997;7:338–344.
Boyer LA, Lee TI, Cole MF, et al. Cell 2005;122:947–956.
Avilion AA, Nicolis SK, Pevny LH, Perez L, Vivian N, Lovell-Badge R. Genes Dev 2003;17:126–140.
Reva T, Clevers H. Nature 2005;434:843–850.
Gil J, Bernard D, Peters G. DNA Cell Biol 2005;24:117–125.
Cayuso J, Marti E. J Neurobiol 2005;64:376–387.
Molotsky AV, Pardal R, Morrison SI. Curr Opin Cell Biol 2004;16:700–707.
Kleber M, Sommer L. Curr Opin Cell Biol 2004;16:681–687.
Kamachi Y, Uchikawa M, Kondoh H. Trends Genet 2000;16:182–187.
Tanaka S, Kamachi Y, Tanouchi A, Hamada H, Iing N, Kondoh H. Mol Cell Biol 2004;24:8834–8846.
Kondoh H, Castro DS, and Guillemot F. Nat Rev Neurosci 2002; 3:517–530.
Lee KJ, Jessell TM. Annu Rev Neurosci 1999;22:261–294.
Shirasaki R, Pfaff SL. Ann Rev Neurosci 2002;25:251–281.
Lee SK, Lee B, Ruiz EC, Pfaff SL. Genes Dev 2005;19:282–294.
Guidato S, Prin F, Guthrie S. Development 2003;130:2981–2996.
Sun T, Pringle NP, Hardy AP, Richardson WD, Smith HK. Mol Cell Neurosci 1998;12:228–239.
Takeuchi K, Mileikovskaia M, Koshiba-Takeuchi K, et al. Development 2005;132:2463–2474.
Thaler JP, Koo SJ, Kania A, et al. Neuron 2004:41:337–350.
Lu QR, Sun T, Zhu Z, et al. Cell 2002;10:75–86.
Novitch BG, Chen AI, Jessell TM. Neuron 2001;31:773–789.
Zhou Q, Anderson DJ. Cell 2002;109:61–73.
Mizuguchi R, Sugimori M, Takebayashi H, et al. Neuron 2001;31: 757–771.
Briscoe J, Pierani A, Jessell TM, Ericson J. Cell 2000;101:435–445.
Thaler JP, Lee SK, Jurata LW, Gill GN, Pfaff SL. Cell 2002;110:237–249.
Zhou Q, Choi G, Anderson DJ. Neuron 2001;31:791–807.
Zhang X, Cai J, Klueber KM, et al. Stem Cells 2005;23:442–453.
Arnett HA, Fancy SP, Alberta JA, et al. Science 2004;306:2111–2115.
Balasubramanivan V, Timmer N, Kust B, Boddeke E, Copray S. Stem Cells 2004;22:878–882.
Buzzard IJ, Gough NM, Crook JM, Colman A. Nat Biotechnol 2004;22:381–382, author reply 382.
Draper IS, Smith K, Gokhale P, et al. Nat Biotechnol 2004;22: 53, 54.
Maitra A, Arking DE, Shivapurkar N, et al. Nat Genet 2005; 37:1099–1103.
Mitalipova MM, Rao RR, Hoyer DM, et al. Nat Biotechnol 2005; 23:19, 20.
Ludwig TE, Levenstein ME, Jones JM, et al. Nat Biotechnol 2006;24:185–187.
Amit M, Carpenter MK, Inokuma MS, et al. Dev Biol 2000;227: 271–278.
Kaneko Y, Sakakibara S, Imai T, et al. Dev Neurosci 2000;22; 139–153.
Lendahl U, Zimmerman LB, McKay RD. Cell 1990;60:585–595.
Okano H, Kawahara H, Toriya M, Nakao K, Shibata S, Imai T. Exp Cell Res 2005;306:349–356.
Knoblich JA. Nat Rev Mol Cell Biol 2001;2:11–20.
Prokopenko SN, Chia W. Semin Cell Dev Biol 2005;16:423–437.
Zhang SC, Wernig M, Duncan ID, Brustle O, Thomson JA. Nat Biotechnol 2001;19:1129–1133.
Zhang SC, Ge B, Duncan ID. Proc Natl Acad Sci USA 1999;96: 4089–4094.
Zhang SC, Ge B, Duncan ID. J Neurosci Res 2000;59;421–429.
Pera MF, Andrade J, Houssami S, et al. J Cell Sci 2004;117: 1269–1280.
Sato N, Meijer L, Skaltsounis L, Greengard P, Brivanlou AH. Nat Med 2004;10:55–63.
Xu RH, Peck RM, Li DS, Feng X, Ludwig T, Thomson JA. Nat Methods 2005;2:185–190.
Gerrard L, Rodgers L, Cui W. Stem Cells 2005;23:1234–1241.
Itsykson P, Ilouz N, Turetsky T, et al. Mol Cell Neurosci 2005;30:24–36.
Xu RH, Chen X, Li DS, et al. Nat Biotechnol 2002;20:1261–1264.
Ying QL, Nichols J, Chambers I, Smith A. Cell 2003a;115:281–292.
Shin S, Mitalipova M, Noggle S, et al. Stem Cells 2006;24:125–138.
Ying QL, Stavridis M, Griffiths D, Li M, Smith A. Nat Biotechnol 2003b;21:183–186.
Li XJ, Du ZW, Zarnowska ED, et al. Nat Biotechnol 2005;23:215–221.
Shin S, Dalton S, Stice SL. Stem Cells Dev 2005;14:266–269.
Copp AJ, Greene ND, Murdoch JN. Nat Rev Genet 2003;4: 784–793.
Wu P, Tarasenko YI, Gu Y, Huang LY, Coggeshall RE, Yu Y. Nat Neurosci 2002;5:1271–1278.
Singh Roy N, Nakano T, Xuing L, Kang J, Nedergaard M, Goldman SA. Exp Neurol 2005;196:224–234.
Wichterle H, Lieberam I, Porter IA, Jessell TM. Cell 2002;110: 385–397.
Arber S, Han B, Mendelsohn M, Smith M, Jessell TM, Sockanathan S. Neuron 1999;23:659–674.
Roy NS, Nakano T, Keyoung HM, et al. Nat Biotechnol 2004; 22:297–305.
Pfaff SL, Mendelsohn M, Stewart CL, Edlund T, Jessell TM. Cell 1996;84:309–320.
Kalb R. Trends Neurosci 2005;28:5–11.
Rao M, Sockanathan S. Science 2005;309:2212–2215.
Nistor GI, Totoiu MO, Haque N, Carpenter MK, Keirstead HS. Glia 2005;49:385–396.
Du ZW, Zhang SC. Stem Cells Dev 2004;13:372–381.
Kilpatrick TJ, Bartlett PF. Neuron 1993;10:255–265.
Rao M. Dev Biol 2004;275:269–286.
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Wilson, P.G., Stice, S.S. Development and differentiation of neural rosettes derived from human embryonic stem cells. Stem Cell Rev 2, 67–77 (2006). https://doi.org/10.1007/s12015-006-0011-1
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DOI: https://doi.org/10.1007/s12015-006-0011-1