Abstract
Human pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), provide a dynamic tool for revealing early embryonic development, modeling pathological processes, and developing therapeutics through drug discovery and potential cell replacement. The first step toward the utilities of human PSCs is directed differentiation to functionally specialized cell/tissue types. Following developmental principles, human ESCs, and lately iPSCs, have been effectively differentiated to region- and/or transmitter-specific neuronal and glial types, including cerebral glutamatergic, striatal γ-aminobutyric acid (GABA)-ergic, forebrain cholinergic, midbrain dopaminergic, and spinal motor neurons, as well as astrocytes and oligodendrocytes. These studies also reveal unique aspects of human cell biology, including intrinsically programmed developmental course, differential uses of transcription factors for neuroectoderm specification, and distinct responses to extracellular signals in regulating cell fate. Such information will be instrumental in translating biological findings to therapeutic development.
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References
Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147
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
Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676
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 131:861–872
Pang ZP, Yang N, Vierbuchen T, Ostermeier A, Fuentes DR, Yang TQ, Citri A, Sebastiano V, Marro S, Sudhof TC, Wernig M (2011) Induction of human neuronal cells by defined transcription factors. Nature [Epub ahead of print]
Pfisterer U, Kirkeby A, Torper O, Wood J, Nelander J, Dufour A, Bjorklund A, Lindvall O, Jakobsson J, Parmar M (2011) Direct conversion of human fibroblasts to dopaminergic neurons. Proc Natl Acad Sci USA 108(25):10343–10348
Stern CD (2005) Neural induction: old problem, new findings, yet more questions. Development 132:2007–2021
Wilson SI, Edlund T (2001) Neural induction: toward a unifying mechanism. Nat Neurosci 4(Suppl):1161–1168
Fuentealba LC, Eivers E, Ikeda A, Hurtado C, Kuroda H, Pera EM, De Robertis EM (2007) Integrating patterning signals: Wnt/GSK3 regulates the duration of the BMP/Smad1 signal. Cell 131:980–993
Aubert J, Dunstan H, Chambers I, Smith A (2002) Functional gene screening in embryonic stem cells implicates Wnt antagonism in neural differentiation. Nat Biotechnol 20:1240–1245
Tropepe V, Hitoshi S, Sirard C, Mak TW, Rossant J, van der Kooy D (2001) Direct neural fate specification from embryonic stem cells: a primitive mammalian neural stem cell stage acquired through a default mechanism. Neuron 30:65–78
Ying QL, Stavridis M, Griffiths D, Li M, Smith A (2003) Conversion of embryonic stem cells into neuroectodermal precursors in adherent monoculture. Nat Biotechnol 21:183–186
Itsykson P, Ilouz N, Turetsky T, Goldstein RS, Pera MF, Fishbein I, Segal M, Reubinoff BE (2005) Derivation of neural precursors from human embryonic stem cells in the presence of noggin. Mol Cell Neurosci 30:24–36
Zhang SC, Wernig M, Duncan ID, Brustle O, Thomson JA (2001) In vitro differentiation of transplantable neural precursors from human embryonic stem cells. Nat Biotechnol 19:1129–1133
Li XJ, Du ZW, Zarnowska ED, Pankratz M, Hansen LO, Pearce RA, Zhang SC (2005) Specification of motoneurons from human embryonic stem cells. Nat Biotechnol 23:215–221
Pera MF, Andrade J, Houssami S, Reubinoff B, Trounson A, Stanley EG, Ward-van Oostwaard D, Mummery C (2004) Regulation of human embryonic stem cell differentiation by BMP-2 and its antagonist noggin. J Cell Sci 117:1269–1280
Lavaute TM, Yoo YD, Pankratz MT, Weick JP, Gerstner JR, Zhang SC (2009) Regulation of neural specification from human embryonic stem cells by BMP and FGF. Stem Cells 27:1741–1749
Pevny L, Placzek M (2005) SOX genes and neural progenitor identity. Curr Opin Neurobiol 15:7–13
Rallu M, Machold R, Gaiano N, Corbin JG, Mcmahon AP, Fishell G (2002) Dorsoventral patterning is established in the telencephalon of mutants lacking both Gli3 and Hedgehog signaling. Development 129:4963–4974
Rash BG, Grove EA (2007) Patterning the dorsal telencephalon: a role for sonic hedgehog? J Neurosci 27:11595–11603
Aoto K, Nishimura T, Eto K, Motoyama J (2002) Mouse GLI3 regulates Fgf8 expression and apoptosis in the developing neural tube, face, and limb bud. Dev Biol 251:320–332
Marti E, Bumcrot DA, Takada R, Mcmahon AP (1995) Requirement of 19 K form of Sonic hedgehog for induction of distinct ventral cell types in CNS explants. Nature 375:322–325
Roelink H, Porter JA, Chiang C, Tanabe Y, Chang DT, Beachy PA, Jessell TM (1995) Floor plate and motor neuron induction by different concentrations of the amino-terminal cleavage product of sonic hedgehog autoproteolysis. Cell 81:445–455
Ericson J, Morton S, Kawakami A, Roelink H, Jessell TM (1996) Two critical periods of sonic hedgehog signaling required for the specification of motor neuron identity. Cell 87:661–673
Temple S (2001) The development of neural stem cells. Nature 414:112–117
Temple S (2001) Stem cell plasticity–building the brain of our dreams. Nat Rev Neurosci 2:513–520
Zhang SC (2006) Neural subtype specification from embryonic stem cells. Brain Pathol 16:132–142
Hu BY, Weick JP, Yu J, Ma LX, Zhang XQ, Thomson JA, Zhang SC (2010) Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency. Proc Natl Acad Sci USA 107:4335–4340
Boulting GL, Kiskinis E, Croft GF, Amoroso MW, Oakley DH, Wainger BJ, Williams DJ, Kahler DJ, Yamaki M, Davidow L, Rodolfa CT, Dimos JT, Mikkilineni S, Macdermott AB, Woolf CJ, Henderson CE, Wichterle H, Eggan K (2011) A functionally characterized test set of human induced pluripotent stem cells. Nat Biotechnol 29:279–286
Chambers SM, Fasano CA, Papapetrou EP, Tomishima M, Sadelain M, Studer L (2009) Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol 27:275–280
Pankratz MT, Li XJ, Lavaute TM, Lyons EA, Chen X, Zhang SC (2007) Directed neural differentiation of human embryonic stem cells via an obligated primitive anterior stage. Stem Cells 25:1511–1520
Zhang X, Huang CT, Chen J, Pankratz MT, Xi J, Li J, Yang Y, Lavaute TM, Li XJ, Ayala M, Bondarenko GI, Du ZW, Jin Y, Golos TG, Zhang SC (2010) Pax6 is a human neuroectoderm cell fate determinant. Cell Stem Cell 7:90–100
Li XJ, Zhang X, Johnson MA, Wang ZB, Lavaute T, Zhang SC (2009) Coordination of sonic hedgehog and Wnt signaling determines ventral and dorsal telencephalic neuron types from human embryonic stem cells. Development 136:4055–4063
Zeng H, Guo M, Martins-Taylor K, Wang X, Zhang Z, Park JW, Zhan S, Kronenberg MS, Lichtler A, Liu HX, Chen FP, Yue L, Li XJ, Xu RH (2010) Specification of region-specific neurons including forebrain glutamatergic neurons from human induced pluripotent stem cells. PLoS One 5:e11853
Elkabetz Y, Panagiotakos G, Al Shamy G, Socci ND, Tabar V, Studer L (2008) Human ES cell-derived neural rosettes reveal a functionally distinct early neural stem cell stage. Genes Dev 22:152–165
Campbell K (2003) Dorsal-ventral patterning in the mammalian telencephalon. Curr Opin Neurobiol 13:50–56
Grove EA, Fukuchi-Shimogori T (2003) Generating the cerebral cortical area map. Annu Rev Neurosci 26:355–380
Gunhaga L, Marklund M, Sjodal M, Hsieh JC, Jessell TM, Edlund T (2003) Specification of dorsal telencephalic character by sequential Wnt and FGF signaling. Nat Neurosci 6:701–707
Stuhmer T, Puelles L, Ekker M, Rubenstein JL (2002) Expression from a Dlx gene enhancer marks adult mouse cortical GABAergic neurons. Cereb Cortex 12:75–85
Olsson M, Campbell K, Turnbull DH (1997) Specification of mouse telencephalic and mid-hindbrain progenitors following heterotopic ultrasound-guided embryonic transplantation. Neuron 19:761–772
Olsson M, Bjorklund A, Campbell K (1998) Early specification of striatal projection neurons and interneuronal subtypes in the lateral and medial ganglionic eminence. Neuroscience 84:867–876
Marin O, Rubenstein JL (2001) A long, remarkable journey: tangential migration in the telencephalon. Nat Rev Neurosci 2:780–790
Eiraku M, Watanabe K, Matsuo-Takasaki M, Kawada M, Yonemura S, Matsumura M, Wataya T, Nishiyama A, Muguruma K, Sasai Y (2008) Self-organized formation of polarized cortical tissues from ESCs and its active manipulation by extrinsic signals. Cell Stem Cell 3:519–532
Gaspard N, Bouschet T, Hourez R, Dimidschstein J, Naeije G, van den Ameele J, Espuny-Camacho I, Herpoel A, Passante L, Schiffmann SN, Gaillard A, Vanderhaeghen P (2008) An intrinsic mechanism of corticogenesis from embryonic stem cells. Nature 455:351–357
Johnson MA, Weick JP, Pearce RA, Zhang SC (2007) Functional neural development from human embryonic stem cells: accelerated synaptic activity via astrocyte coculture. J Neurosci 27:3069–3077
Letinic K, Zoncu R, Rakic P (2002) Origin of GABAergic neurons in the human neocortex. Nature 417:645–649
Tan SS, Kalloniatis M, Sturm K, Tam PP, Reese BE, Faulkner-Jones B (1998) Separate progenitors for radial and tangential cell dispersion during development of the cerebral neocortex. Neuron 21:295–304
Anderson S, Mione M, Yun K, Rubenstein JL (1999) Differential origins of neocortical projection and local circuit neurons: role of Dlx genes in neocortical interneuronogenesis. Cereb Cortex 9:646–654
Casarosa S, Fode C, Guillemot F (1999) Mash1 regulates neurogenesis in the ventral telencephalon. Development 126:525–534
Horton S, Meredith A, Richardson JA, Johnson JE (1999) Correct coordination of neuronal differentiation events in ventral forebrain requires the bHLH factor MASH1. Mol Cell Neurosci 14:355–369
Aubry L, Bugi A, Lefort N, Rousseau F, Peschanski M, Perrier AL (2008) Striatal progenitors derived from human ES cells mature into DARPP32 neurons in vitro and in quinolinic acid-lesioned rats. Proc Natl Acad Sci USA 105:16707–16712
Ma LX, Hu B, Liu Y, Liu H, Vermilyea SC, Liu H, Zhang X, Sun Y, Gao L, Li J, Ayala M, Zhang SC (2010) Specification of functional striatal GABAergic projection neurons from human stem cells. Soc Neurosci Abstr 331:7
Liu Y, Krencik R, Liu H, Ma LX, Zhang X, Zhang SC (2010) Functional cholinergic neurons from human embryonic stem cells. Soc Neurosci Abstr 331:5
Bissonnette CJ, Lyass L, Bhattacharyya BJ, Belmadani A, Miller RJ, Kessler JA (2011) The controlled generation of functional basal forebrain cholinergic neurons from human embryonic stem cells. Stem Cells 29(5):802–811
Nilbratt M, Porras O, Marutle A, Hovatta O, Nordberg A (2010) Neurotrophic factors promote cholinergic differentiation in human embryonic stem cell-derived neurons. J Cell Mol Med 14:1476–1484
Singh Roy N, Nakano T, Xuing L, Kang J, Nedergaard M, Goldman SA (2005) Enhancer-specified GFP-based FACS purification of human spinal motor neurons from embryonic stem cells. Exp Neurol 196:224–234
Hu BY, Zhang SC (2009) Differentiation of spinal motor neurons from pluripotent human stem cells. Nat Protoc 4:1295–1304
Lee H, Shamy GA, Elkabetz Y, Schofield CM, Harrsion NL, Panagiotakos G, Socci ND, Tabar V, Studer L (2007) Directed differentiation and transplantation of human embryonic stem cell-derived motoneurons. Stem Cells 25:1931–1939
Dimos JT, Rodolfa KT, Niakan KK, Weisenthal LM, Mitsumoto H, Chung W, Croft GF, Saphier G, Leibel R, Goland R, Wichterle H, Henderson CE, Eggan K (2008) Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 321:1218–1221
Ebert AD, Yu J, Rose FF Jr, Mattis VB, Lorson CL, Thomson JA, Svendsen CN (2009) Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature 457:277–280
Li XJ, Hu BY, Jones SA, Zhang YS, Lavaute T, Du ZW, Zhang SC (2008) Directed differentiation of ventral spinal progenitors and motor neurons from human embryonic stem cells by small molecules. Stem Cells 26:886–893
Patani R, Hollins AJ, Wishart TM, Puddifoot CA, Alvarez S, de Lera AR, Wyllie DJ, Compston DA, Pedersen RA, Gillingwater TH, Hardingham GE, Allen ND, Chandran S (2011) Retinoid-independent motor neurogenesis from human embryonic stem cells reveals a medial columnar ground state. Nat Commun 2:214
Bjorklund A, Lindvall O (2000) Cell replacement therapies for central nervous system disorders. Nat Neurosci 3:537–544
Freed CR, Greene PE, Breeze RE, Tsai WY, Dumouchel W, Kao R, Dillon S, Winfield H, Culver S, Trojanowski JQ, Eidelberg D, Fahn S (2001) Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N Engl J Med 344:710–719
Olanow CW, Goetz CG, Kordower JH, Stoessl AJ, Sossi V, Brin MF, Shannon KM, Nauert GM, Perl DP, Godbold J, Freeman TB (2003) A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson’s disease. Ann Neurol 54:403–414
Yang D, Zhang ZJ, Oldenburg M, Ayala M, Zhang SC (2008) Human embryonic stem cell-derived dopaminergic neurons reverse functional deficit in parkinsonian rats. Stem Cells 26:55–63
Yan Y, Yang D, Zarnowska ED, Du Z, Werbel B, Valliere C, Pearce RA, Thomson JA, Zhang SC (2005) Directed differentiation of dopaminergic neuronal subtypes from human embryonic stem cells. Stem Cells 23:781–790
Zeng X, Cai J, Chen J, Luo Y, You ZB, Fotter E, Wang Y, Harvey B, Miura T, Backman C, Chen GJ, Rao MS, Freed WJ (2004) Dopaminergic differentiation of human embryonic stem cells. Stem Cells 22:925–940
Schulz TC, Noggle SA, Palmarini GM, Weiler DA, Lyons IG, Pensa KA, Meedeniya AC, Davidson BP, Lambert NA, Condie BG (2004) Differentiation of human embryonic stem cells to dopaminergic neurons in serum-free suspension culture. Stem Cells 22:1218–1238
Perrier AL, Tabar V, Barberi T, Rubio ME, Bruses J, Topf N, Harrison NL, Studer L (2004) Derivation of midbrain dopamine neurons from human embryonic stem cells. Proc Natl Acad Sci USA 101:12543–12548
Park CH, Minn YK, Lee JY, Choi DH, Chang MY, Shim JW, Ko JY, Koh HC, Kang MJ, Kang JS, Rhie DJ, Lee YS, Son H, Moon SY, Kim KS, Lee SH (2005) In vitro and in vivo analyses of human embryonic stem cell-derived dopamine neurons. J Neurochem 92:1265–1276
Sonntag KC, Pruszak J, Yoshizaki T, van Arensbergen J, Sanchez-Pernaute R, Isacson O (2007) Enhanced yield of neuroepithelial precursors and midbrain-like dopaminergic neurons from human embryonic stem cells using the bone morphogenic protein antagonist noggin. Stem Cells 25:411–418
Roy NS, Cleren C, Singh SK, Yang L, Beal MF, Goldman SA (2006) Functional engraftment of human ES cell-derived dopaminergic neurons enriched by coculture with telomerase-immortalized midbrain astrocytes. Nat Med 12:1259–1268
Young A, Assey KS, Sturkie CD, West FD, Machacek DW, Stice SL (2010) Glial cell line-derived neurotrophic factor enhances in vitro differentiation of mid-/hindbrain neural progenitor cells to dopaminergic-like neurons. J Neurosci Res 88:3222–3232
Swistowski A, Peng J, Liu Q, Mali P, Rao MS, Cheng L, Zeng X (2010) Efficient generation of functional dopaminergic neurons from human induced pluripotent stem cells under defined conditions. Stem Cells 28:1893–1904
Hargus G, Cooper O, Deleidi M, Levy A, Lee K, Marlow E, Yow A, Soldner F, Hockemeyer D, Hallett PJ, Osborn T, Jaenisch R, Isacson O (2010) Differentiated Parkinson patient-derived induced pluripotent stem cells grow in the adult rodent brain and reduce motor asymmetry in Parkinsonian rats. Proc Natl Acad Sci USA 107:15921–15926
Weick JP, Johnson MA, Skroch SP, Williams JC, Deisseroth K, Zhang SC (2010) Functional control of transplantable human ESC-derived neurons via optogenetic targeting. Stem Cells 28:2008–2016
Boyden ES, Zhang F, Bamberg E, Nagel G, Deisseroth K (2005) Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci 8:1263–1268
Ono Y, Nakatani T, Sakamoto Y, Mizuhara E, Minaki Y, Kumai M, Hamaguchi A, Nishimura M, Inoue Y, Hayashi H, Takahashi J, Imai T (2007) Differences in neurogenic potential in floor plate cells along an anteroposterior location: midbrain dopaminergic neurons originate from mesencephalic floor plate cells. Development 134:3213–3225
Fasano CA, Chambers SM, Lee G, Tomishima MJ, Studer L (2010) Efficient derivation of functional floor plate tissue from human embryonic stem cells. Cell Stem Cell 6:336–347
Denham M, Thompson LH, Leung J, Pebay A, Bjorklund A, Dottori M (2010) Gli1 is an inducing factor in generating floor plate progenitor cells from human embryonic stem cells. Stem Cells 28:1805–1815
Cooper O, Hargus G, Deleidi M, Blak A, Osborn T, Marlow E, Lee K, Levy A, Perez-Torres E, Yow A, Isacson O (2010) Differentiation of human ES and Parkinson’s disease iPS cells into ventral midbrain dopaminergic neurons requires a high activity form of SHH, FGF8a and specific regionalization by retinoic acid. Mol Cell Neurosci 45:258–266
Soldner F, Hockemeyer D, Beard C, Gao Q, Bell GW, Cook EG, Hargus G, Blak A, Cooper O, Mitalipova M, Isacson O, Jaenisch R (2009) Parkinson’s disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell 136:964–977
Zhang SC (2001) Defining glial cells during CNS development. Nat Rev Neurosci 2:840–843
Rowitch DH (2004) Glial specification in the vertebrate neural tube. Nat Rev Neurosci 5:409–419
Carpenter MK, Inokuma MS, Denham J, Mujtaba T, Chiu CP, Rao MS (2001) Enrichment of neurons and neural precursors from human embryonic stem cells. Exp Neurol 172:383–397
Deneen B, Ho R, Lukaszewicz A, Hochstim CJ, Gronostajski RM, Anderson DJ (2006) The transcription factor NFIA controls the onset of gliogenesis in the developing spinal cord. Neuron 52:953–968
Krencik R, Weick JH, Zhang Z, Zhang SC (2011) Specification of transplantable astroglial cells from human pluripotent stem cells. Nat Biotechnol 29:528–534
Castelo-Branco G, Sousa KM, Bryja V, Pinto L, Wagner J, Arenas E (2006) Ventral midbrain glia express region-specific transcription factors and regulate dopaminergic neurogenesis through Wnt-5a secretion. Mol Cell Neurosci 31:251–262
Wagner J, Akerud P, Castro DS, Holm PC, Canals JM, Snyder EY, Perlmann T, Arenas E (1999) Induction of a midbrain dopaminergic phenotype in Nurr1-overexpressing neural stem cells by type 1 astrocytes. Nat Biotechnol 17:653–659
Richardson WD, Kessaris N, Pringle N (2006) Oligodendrocyte wars. Nat Rev Neurosci 7:11–18
Hu BY, Du ZW, Li XJ, Ayala M, Zhang SC (2009) Human oligodendrocytes from embryonic stem cells: conserved SHH signaling networks and divergent FGF effects. Development 136:1443–1452
Hu BY, Du ZW, Zhang SC (2009) Differentiation of human oligodendrocytes from pluripotent stem cells. Nat Protoc 4:1614–1622
Brustle O, Jones KN, Learish RD, Karram K, Choudhary K, Wiestler OD, Duncan ID, Mckay RD (1999) Embryonic stem cell-derived glial precursors: a source of myelinating transplants. Science 285:754–756
Billon N, Jolicoeur C, Ying QL, Smith A, Raff M (2002) Normal timing of oligodendrocyte development from genetically engineered, lineage-selectable mouse ES cells. J Cell Sci 115:3657–3665
Mcdonald JW, Liu XZ, Qu Y, Liu S, Mickey SK, Turetsky D, Gottlieb DI, Choi DW (1999) Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord. Nat Med 5:1410–1412
Mcmorris FA, Mckinnon RD (1996) Regulation of oligodendrocyte development and CNS myelination by growth factors: prospects for therapy of demyelinating disease. Brain Pathol 6:313–329
Zhang SC, Ge B, Duncan ID (2000) Tracing human oligodendroglial development in vitro. J Neurosci Res 59:421–429
Grever WE, Zhang S, Ge B, Duncan ID (1999) Fractionation and enrichment of oligodendrocytes from developing human brain. J Neurosci Res 57:304–314
Chandran S, Compston A (2005) Neural stem cells as a potential source of oligodendrocytes for myelin repair. J Neurol Sci 233:179–181
Chandran S, Compston A, Jauniaux E, Gilson J, Blakemore W, Svendsen C (2004) Differential generation of oligodendrocytes from human and rodent embryonic spinal cord neural precursors. Glia 47:314–324
Izrael M, Zhang P, Kaufman R, Shinder V, Ella R, Amit M, Itskovitz-Eldor J, Chebath J, Revel M (2007) Human oligodendrocytes derived from embryonic stem cells: effect of noggin on phenotypic differentiation in vitro and on myelination in vivo. Mol Cell Neurosci 34:310–323
Kang SM, Cho MS, Seo H, Yoon CJ, Oh SK, Choi YM, Kim DW (2007) Efficient induction of oligodendrocytes from human embryonic stem cells. Stem Cells 25:419–424
Nistor GI, Totoiu MO, Haque N, Carpenter MK, Keirstead HS (2005) Human embryonic stem cells differentiate into oligodendrocytes in high purity and myelinate after spinal cord transplantation. Glia 49:385–396
Zuber ME, Gestri G, Viczian AS, Barsacchi G, Harris WA (2003) Specification of the vertebrate eye by a network of eye field transcription factors. Development 130:5155–5167
Mathers PH, Jamrich M (2000) Regulation of eye formation by the Rx and pax6 homeobox genes. Cell Mol Life Sci 57:186–194
Osakada F, Ikeda H, Mandai M, Wataya T, Watanabe K, Yoshimura N, Akaike A, Sasai Y, Takahashi M (2008) Toward the generation of rod and cone photoreceptors from mouse, monkey and human embryonic stem cells. Nat Biotechnol 26:215–224
Meyer JS, Shearer RL, Capowski EE, Wright LS, Wallace KA, Mcmillan EL, Zhang SC, Gamm DM (2009) Modeling early retinal development with human embryonic and induced pluripotent stem cells. Proc Natl Acad Sci USA 106:16698–16703
Klimanskaya I, Hipp J, Rezai KA, West M, Atala A, Lanza R (2004) Derivation and comparative assessment of retinal pigment epithelium from human embryonic stem cells using transcriptomics. Cloning Stem Cells 6:217–245
Kagiyama Y, Gotouda N, Sakagami K, Yasuda K, Mochii M, Araki M (2005) Extraocular dorsal signal affects the developmental fate of the optic vesicle and patterns the optic neuroepithelium. Dev Growth Differ 47:523–536
Reh TA, Lamba D, Gust J (2010) Directing human embryonic stem cells to a retinal fate. Methods Mol Biol 636:139–153
Idelson M, Alper R, Obolensky A, Ben-Shushan E, Hemo I, Yachimovich-Cohen N, Khaner H, Smith Y, Wiser O, Gropp M, Cohen MA, Even-Ram S, Berman-Zaken Y, Matzrafi L, Rechavi G, Banin E, Reubinoff B (2009) Directed differentiation of human embryonic stem cells into functional retinal pigment epithelium cells. Cell Stem Cell 5:396–408
Osakada F, Jin ZB, Hirami Y, Ikeda H, Danjyo T, Watanabe K, Sasai Y, Takahashi M (2009) In vitro differentiation of retinal cells from human pluripotent stem cells by small-molecule induction. J Cell Sci 122:3169–3179
Carr AJ, Vugler AA, Hikita ST, Lawrence JM, Gias C, Chen LL, Buchholz DE, Ahmado A, Semo M, Smart MJ, Hasan S, Da Cruz L, Johnson LV, Clegg DO, Coffey PJ (2009) Protective effects of human iPS-derived retinal pigment epithelium cell transplantation in the retinal dystrophic rat. PLoS One 4:e8152
Kokkinaki M, Sahibzada N, Golestaneh N (2011) Human iPS-derived retinal pigment epithelium (RPE) cells exhibit ion transport, membrane potential, polarized VEGF secretion and gene expression pattern similar to native RPE. Stem Cells 29:825–835
Amirpour N, Karamali F, Rabiee F, Rezaei L, Esfandiari E, Razavi S, Dehghani A, Razmju H, Nasr-Esfahani MH, Baharvand H (2011) Differentiation of human embryonic stem cell-derived retinal progenitors into retinal cells by sonic hedgehog and/or retinal pigmented epithelium and transplantation into the subretinal space of sodium iodate-injected rabbits. Stem Cells Dev Jun 1. (Epub ahead of print)
Muotri AR, Nakashima K, Toni N, Sandler VM, Gage FH (2005) Development of functional human embryonic stem cell-derived neurons in mouse brain. Proc Natl Acad Sci USA 102:18644–18648
Darsalia V, Allison SJ, Cusulin C, Monni E, Kuzdas D, Kallur T, Lindvall O, Kokaia Z (2011) Cell number and timing of transplantation determine survival of human neural stem cell grafts in stroke-damaged rat brain. J Cereb Blood Flow Metab 31:235–242
Acknowledgments
The authors thank members of the Zhang laboratory for reading and commenting on the manuscript. Studies presented from our laboratory have been supported by the National Institute of Neurological Disorders and Stroke (NS045926, NS057778, NS064578), ALS Association, National MS Society (NMSS TR-3761), NYSTEM (C024406), Bleser Family Foundation, Busta Family Foundation, Neuroscience Training Program (T32 GM007507) and partly by a core grant to the Waisman Center from the National Institute of Child Health and Human Development (P30 HD03352).
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Liu, H., Zhang, SC. Specification of neuronal and glial subtypes from human pluripotent stem cells. Cell. Mol. Life Sci. 68, 3995–4008 (2011). https://doi.org/10.1007/s00018-011-0770-y
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DOI: https://doi.org/10.1007/s00018-011-0770-y