Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling
Open accessAbstract
Current neural induction protocols for human embryonic stem (hES) cells rely on embryoid body formation, stromal feeder co-culture or selective survival conditions. Each strategy has considerable drawbacks, such as poorly defined culture conditions, protracted differentiation and low yield. Here we report that the synergistic action of two inhibitors of SMAD signaling, Noggin and SB431542, is sufficient to induce rapid and complete neural conversion of >80% of hES cells under adherent culture conditions. Temporal fate analysis reveals the appearance of a transient FGF5(+) epiblast-like stage followed by PAX6(+) neural cells competent to form rosettes. Initial cell density determines the ratio of central nervous system and neural crest progeny. Directed differentiation of human induced pluripotent stem (hiPS) cells into midbrain dopamine and spinal motoneurons confirms the robustness and general applicability of the induction protocol. Noggin/SB431542-based neural induction should facilitate the use of hES and hiPS cells in regenerative medicine and disease modeling and obviate the need for protocols based on stromal feeders or embryoid bodies.
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Noggin is essential for neural lineage induction via bone morphogenic protein (BMP) antagonism.
“Noggin is essential for neural lineage induction via bone morphogenic protein (BMP) antagonism (Chambers et al., 2009).”
From Challenges and solutions in transitioning to animal-free standards: a comprehensive analysis of components in human cell-based developmental neurotoxicity assays (2026) · cites this paper as Chambers et al., 2009
The supplied passages labeled Abstract say Noggin represses endogenous BMP signals and, with SB431542, promotes efficient neural conversion of human pluripotent cells. They do not establish that Noggin is essential for neural lineage induction generally; the paper says Noggin alone is insufficient under its defined culture conditions. (LLM, conf=0.88)
Experimental — accuracy not yet measuredNeural induction in brain organoids commonly includes SMAD signalling inhibition followed by specific morphogens and fate-specifying molecules.
“Commonly, neural induction in brain organoids includes inhibition of SMAD signalling to inhibit mesoderm and endoderm formation, followed by the provision of specific morphogens and fate-specifying molecules18.”
From The use of brain organoids to investigate neural development and disease (2017) · cites this paper as [18]
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Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors
Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007) · Cell · doi:10.1016/j.cell.2007.11.019 · Cited by 20,221 · see citing works
Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells
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., et al. (2007) · Science · doi:10.1126/science.1151526 · Cited by 10,310 · see citing works
Reprogramming of human somatic cells to pluripotency with defined factors
Park, I.-H., Zhao, R., West, J. A., Yabuuchi, A., Huo, H.-G., Ince, T., Lerou, P., Lensch, M., & Daley, G. Q. (2008) · Nature · doi:10.1038/nature06534 · Cited by 3,028 · see citing works
Laflamme, M. A., Chen, K. Y., Naumova, A. V., Muskheli, V., Fugate, J. A., Dupras, S. K., Reinecke, H., Xu, C., Hassanipour, M., Police, S., et al. (2007) · Nature Biotechnology · doi:10.1038/nbt1327 · Cited by 2,207 · see citing works
New cell lines from mouse epiblast share defining features with human embryonic stem cells
Tesar, P. J., Chenoweth, J. G., Brook, F. A., Davies, T. J., Evans, E. P., Mack, D. L., Gardner, R. L., & McKay, R. D. G. (2007) · Nature · doi:10.1038/nature05972 · Cited by 2,153 · see citing works
A ROCK inhibitor permits survival of dissociated human embryonic stem cells
Watanabe, K., Ueno, M., Kamiya, D., Nishiyama, A., Matsumura, M., Wataya, T., Takahashi, J. B., Nishikawa, S., Nishikawa, S.-I., Muguruma, K., et al. (2007) · Nature Biotechnology · doi:10.1038/nbt1310 · Cited by 2,055 · see citing works
Efficient differentiation of human embryonic stem cells to definitive endoderm
D'Amour, K. A., Agulnick, A. D., Eliazer, S., Kelly, O. G., Kroon, E., & Baetge, E. E. (2005) · Nature Biotechnology · doi:10.1038/nbt1163 · Cited by 1,730 · see citing works
Induction of Midbrain Dopaminergic Neurons from ES Cells by Stromal Cell–Derived Inducing Activity
Kawasaki, H., Mizuseki, K., Nishikawa, S., Kaneko, S., Kuwana, Y., Nakanishi, S., Nishikawa, S., & Sasai, Y. (2000) · Neuron · doi:10.1016/s0896-6273(00)00083-0 · Cited by 1,277 · see citing works
Smith, W. C., & Harland, R. M. (1992) · Cell · doi:10.1016/0092-8674(92)90316-5 · Cited by 1,184 · see citing works
Xenopus chordin: A novel dorsalizing factor activated by organizer-specific homeobox genes
Sasai, Y. (1994) · Cell · doi:10.1016/0092-8674(94)90068-x · Cited by 1,122 · see citing works
BMP4 initiates human embryonic stem cell differentiation to trophoblast
Xu, R., Chen, X., Li, D. S., Li, R., Addicks, G. C., Glennon, C., Zwaka, T. P., & Thomson, J. A. (2002) · Nature Biotechnology · doi:10.1038/nbt761 · Cited by 1,118 · see citing works
Derivation of midbrain dopamine neurons from human embryonic stem cells
Perrier, A. L., Tabar, V. S., Barberi, T., Rubio, M. E., Brusés, J. L., Topf, N., Harrison, N. L., & Studer, L. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0404700101 · Cited by 981 · see citing works
Self-citationSpecification of motoneurons from human embryonic stem cells
Li, X. J., Du, Z.-W., Żarnowska, E. D., Pankratz, M. T., Hansen, L., Pearce, R. A., & Zhang, S. (2005) · Nature Biotechnology · doi:10.1038/nbt1063 · Cited by 767 · see citing works
Hemmati‐Brivanlou, A., Kelly, O., & Melton, D. A. (1994) · Cell · doi:10.1016/0092-8674(94)90320-4 · Cited by 761 · see citing works
Human ES cell-derived neural rosettes reveal a functionally distinct early neural stem cell stage
Elkabetz, Y., Panagiotakos, G., Al Shamy, G., Socci, N. D., Tabar, V., & Studer, L. (2008) · Genes & Development · doi:10.1101/gad.1616208 · Cited by 677 · see citing works
Self-citationNeural induction, the default model and embryonic stem cells
Muñoz-Sanjuán, I., & Brivanlou, A. H. (2002) · Nature reviews. Neuroscience · doi:10.1038/nrn786 · Cited by 635 · see citing works
NANOG Is a Direct Target of TGFβ/Activin-Mediated SMAD Signaling in Human ESCs
Xu, R., Sampsell-Barron, T. L., Gu, F., Root, S. H., Peck, R. M., Pan, G., Yu, J., Antosiewicz‐Bourget, J., Tian, S., Stewart, R. M., et al. (2008) · Cell stem cell · doi:10.1016/j.stem.2008.07.001 · Cited by 512 · see citing works
PAX-6IN DEVELOPMENT AND EVOLUTION
Callaerts, P., Halder, G. A., & Gehring, W. J. (1997) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.20.1.483 · Cited by 456 · see citing works
Directed Differentiation and Transplantation of Human Embryonic Stem Cell-Derived Motoneurons
Lee, H., Al-Shamy, G., Elkabetz, Y., Schofield, C. M., Harrsion, N. L., Panagiotakos, G., Socci, N. D., Tabar, V. S., & Studer, L. (2007) · Stem Cells · doi:10.1634/stemcells.2007-0097 · Cited by 351 · see citing works
Self-citationSmith, J. R., Vallier, L., Lupo, G., Alexander, M., Harris, W. A., & Pedersen, R. A. (2007) · Developmental Biology · doi:10.1016/j.ydbio.2007.10.003 · Cited by 295 · see citing works
Identification of mammalian noggin and its expression in the adult nervous system
Valenzuela, D., Economides, A. N., Rojas, E., Lamb, T., Nunez, L., Jones, P., Lp, N., Espinosa, R., Brannan, C., & Gilbert, D. J. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-09-06077.1995 · Cited by 135 · see citing works
Suter, D. M., Tirefort, D., Julien, S., & Krause, K. (2008) · Stem Cells · doi:10.1634/stemcells.2008-0319 · Cited by 121 · see citing works
BAC Transgenesis in Human Embryonic Stem Cells as a Novel Tool to Define the Human Neural Lineage
Placantonakis, D. G., Tomishima, M. J., Lafaille, F. G., Desbordes, S. C., Jia, F., Socci, N. D., Viale, A. J., Lee, H., Harrison, N. L., Tabar, V. S., et al. (2008) · Stem Cells · doi:10.1634/stemcells.2008-0884 · Cited by 81 · see citing works
Self-citationTomishima, M. J., Hadjantonakis, A., Gong, S., & Studer, L. (2006) · Stem Cells · doi:10.1634/stemcells.2006-0173 · Cited by 36 · see citing works
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Flagged first, then by citations
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Sorted by citations
Kriks, S., Shim, J., Piao, J., Ganat, Y. M., Wakeman, D. R., Xie, Z., Carrillo‐Reid, L., Auyeung, G., Antonacci, C. L., Buch, A., et al. (2011) · Nature · doi:10.1038/nature10648 · Cited by 1,912 · see citing works
Self-citationRapid single-step induction of functional neurons from human pluripotent stem cells
Zhang, Y., Pak, C., Han, Y., Ahlenius, H., Zhang, Z., Chanda, S., Marro, S., Patzke, C., Acuna, C., Covy, J., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.05.029 · Cited by 1,644 · see citing works
Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture
Paşca, A. M., Sloan, S. A., Clarke, L. E., Tian, Y., Makinson, C. D., Huber, N., Kim, C. H., Park, J.-Y., O'Rourke, N. A., Nguyen, K. D., et al. (2015) · Nature Methods · doi:10.1038/nmeth.3415 · Cited by 1,609 · see citing works
Shi, Y., Kirwan, P., & Livesey, F. J. (2012) · Nature Protocols · doi:10.1038/nprot.2012.116 · Cited by 972 · see citing works
Hu, B., Weick, J. P., Yu, J., Ma, L., Zhang, X., Thomson, J. A., & Zhang, S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910012107 · Cited by 1,007 · see citing works
A method to recapitulate early embryonic spatial patterning in human embryonic stem cells
Warmflash, A., Sorre, B., Etoc, F., Siggia, E. D., & Brivanlou, A. H. (2014) · Nature Methods · doi:10.1038/nmeth.3016 · Cited by 885 · see citing works
Resetting Transcription Factor Control Circuitry toward Ground-State Pluripotency in Human
Takashima, Y., Guo, G., Loos, R., Nichols, J., Ficz, G., Krueger, F., Oxley, D., Santos, F., Clarke, J., Mansfield, W., et al. (2014) · Cell · doi:10.1016/j.cell.2014.08.029 · Cited by 980 · see citing works
Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs
Lee, G., Papapetrou, E. P., Kim, H., Chambers, S. M., Tomishima, M. J., Fasano, C. A., Ganat, Y. M., Menon, J., Shimizu, F., Viale, A. J., et al. (2009) · Nature · doi:10.1038/nature08320 · Cited by 867 · see citing works
Self-citationEngineering Stem Cell Organoids
Yin, X., Mead, B. E., Safaee, H., Langer, R., Karp, J. M., & Levy, O. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2015.12.005 · Cited by 866 · see citing works
Jo, J., Xiao, Y., Sun, A. X., Cukuroglu, E., Tran, H.-D., Göke, J., Tan, Z. Y., Saw, T. Y., Tan, C.-P., Lokman, H., et al. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.07.005 · Cited by 861 · see citing works
G&T-seq: parallel sequencing of single-cell genomes and transcriptomes
Macaulay, I. C., Haerty, W., Kumar, P., Li, Y. I., Hu, T. X., Teng, M. J., Goolam, M., Saurat, N., Coupland, P., Shirley, L. M., et al. (2015) · Nature Methods · doi:10.1038/nmeth.3370 · Cited by 750 · see citing works
In vitro generation of human pluripotent stem cell derived lung organoids
Dye, B. R., Hill, D. R., Ferguson, M. A. H., Tsai, Y.-H., Nagy, M. S., Dyal, R., Wells, J. M., Mayhew, C. N., Nattiv, R., Klein, O. D., et al. (2015) · eLife · doi:10.7554/elife.05098 · Cited by 824 · see citing works
Human cerebral cortex development from pluripotent stem cells to functional excitatory synapses
Shi, Y., Kirwan, P., Smith, J., Robinson, H. P. C., & Livesey, F. J. (2012) · Nature Neuroscience · doi:10.1038/nn.3041 · Cited by 813 · see citing works
The use of brain organoids to investigate neural development and disease
Di Lullo, E., & Kriegstein, A. R. (2017) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.107 · Cited by 788 · see citing works
LRRK2 Mutant iPSC-Derived DA Neurons Demonstrate Increased Susceptibility to Oxidative Stress
Nguyen, H. N., Byers, B., Cord, B. J., Shcheglovitov, A., Byrne, J., Gujar, P., Kee, K., Schüle, B., Dolmetsch, R. E., Langston, J. W., et al. (2011) · Cell stem cell · doi:10.1016/j.stem.2011.01.013 · Cited by 748 · see citing works
Epigenomic Analysis of Multilineage Differentiation of Human Embryonic Stem Cells
Xie, W., Schultz, M. D., Lister, R., Hou, Z., Rajagopal, N., Ray, P. R., Whitaker, J. W., Tian, S., Hawkins, R. D., Leung, D., et al. (2013) · Cell · doi:10.1016/j.cell.2013.04.022 · Cited by 721 · see citing works
Xiang, Y., Tanaka, Y., Patterson, B., Kang, Y., Govindaiah, G., Roselaar, N., Çakır, B., Kim, K.-Y., Lombroso, A., Hwang, S., et al. (2017) · Cell stem cell · doi:10.1016/j.stem.2017.07.007 · Cited by 696 · see citing works
Human iPS cell-derived dopaminergic neurons function in a primate Parkinson’s disease model
Kikuchi, T., Morizane, A., Doi, D., Magotani, H., Onoe, H., Hayashi, T., Mizuma, H., Takara, S., Takahashi, R., Inoue, H., et al. (2017) · Nature · doi:10.1038/nature23664 · Cited by 702 · see citing works
Kirkeby, A., Grealish, S., Wolf, D. A., Nelander, J., Wood, J., Lundblad, M., Lindvall, O., & Parmar, M. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.04.009 · Cited by 662 · see citing works
Intrinsic Membrane Hyperexcitability of Amyotrophic Lateral Sclerosis Patient-Derived Motor Neurons
Wainger, B. J., Kiskinis, E., Mellin, C., Wiskow, O., Han, S. S. W., Sandoe, J., Perez, N. P., Williams, L. A., Lee, S., Boulting, G. L., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.03.019 · Cited by 652 · see citing works
The Cell-Cycle State of Stem Cells Determines Cell Fate Propensity
Pauklin, S., & Vallier, L. (2013) · Cell · doi:10.1016/j.cell.2013.08.031 · Cited by 611 · see citing works
Microglia innately develop within cerebral organoids
Ormel, P. R., de Sá, R. V., van Bodegraven, E. J., Karst, H., Harschnitz, O., Sneeboer, M. A. M., Johansen, L. E., van Dijk, R. E., Scheefhals, N., van Berlekom, A. B., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06684-2 · Cited by 624 · see citing works
Chambers, S. M., Qi, Y., Mica, Y., Lee, G., Zhang, X., Niu, L., Bilsland, J., Cao, L., Stevens, E. B., Whiting, P. J., et al. (2012) · Nature Biotechnology · doi:10.1038/nbt.2249 · Cited by 605 · see citing works
Self-citationMaroof, A. M., Keros, S., Tyson, J. A., Ying, S.-W., Ganat, Y. M., Merkle, F. T., Liu, B., Goulburn, A., Stanley, E. G., Elefanty, A. G., et al. (2013) · Cell Stem Cell · doi:10.1016/j.stem.2013.04.008 · Cited by 596 · see citing works
Self-citationSloan, S. A., Darmanis, S., Huber, N., Khan, T. A., Birey, F., Caneda, C., Reimer, R., Quake, S. R., Barres, B. A., & Paşca, S. P. (2017) · Neuron · doi:10.1016/j.neuron.2017.07.035 · Cited by 593 · see citing works
Wang, S., Bates, J., Li, X., Schanz, S., Chandler-Militello, D., Levine, C., Maherali, N., Studer, L., Hochedlinger, K., Windrem, M., et al. (2013) · Cell Stem Cell · doi:10.1016/j.stem.2012.12.002 · Cited by 586 · see citing works
Self-citationEspuny-Camacho, I., Michelsen, K. A., Gall, D., Linaro, D., Hasche, A., Bonnefont, J., Bali, C., Orduz, D., Bilheu, A., Herpoel, A., et al. (2013) · Neuron · doi:10.1016/j.neuron.2012.12.011 · Cited by 568 · see citing works
Chu, L.-F., Leng, N., Zhang, J., Hou, Z., Mamott, D., Vereide, D. T., Choi, J., Kendziorski, C., Stewart, R., & Thomson, J. A. (2016) · Genome Biology · doi:10.1186/s13059-016-1033-x · Cited by 477 · see citing works
Transcription factor-mediated differentiation of human iPSCs into neurons
Fernandopulle, M. S., Prestil, R., Grunseich, C., Wang, C., Gan, L., & Ward, M. E. (2018) · Current Protocols in Cell Biology · doi:10.1002/cpcb.51 · Cited by 461 · see citing works
Human ADAR1 Prevents Endogenous RNA from Triggering Translational Shutdown
Chung, H., Calis, J. J. A., Wu, X., Sun, T., Yu, Y., Sarbanes, S. L., Dao Thi, V. L., Shilvock, A. R., Hoffmann, H.-H., Rosenberg, B. R., et al. (2018) · Cell · doi:10.1016/j.cell.2017.12.038 · Cited by 538 · see citing works
Nicholas, C. R., Chen, J., Tang, Y., Southwell, D. G., Chalmers, N., Vogt, D. L., Arnold, C. M., Chen, Y.-J. J., Stanley, E. G., Elefanty, A. G., et al. (2013) · Cell stem cell · doi:10.1016/j.stem.2013.04.005 · Cited by 513 · see citing works
Generation of human brain region–specific organoids using a miniaturized spinning bioreactor
Qian, X., Jacob, F., Song, M. M., Nguyen, H. N., Song, H., & Ming, G. (2018) · Nature Protocols · doi:10.1038/nprot.2017.152 · Cited by 515 · see citing works
Rescue of Fragile X Syndrome Neurons by DNA Methylation Editing of the FMR1 Gene
Liu, X. S., Wu, H., Krzisch, M., Wu, X., Graef, J. D., Muffat, J., Hnisz, D., Li, C. H., Yuan, B., Xu, C., et al. (2018) · Cell · doi:10.1016/j.cell.2018.01.012 · Cited by 506 · see citing works
Ludtmann, M. H. R., Angelova, P. R., Horrocks, M. H., Choi, M. L., Rodrigues, M., Baev, A. Y., Berezhnov, A. V., Yao, Z., Little, D., Banushi, B., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04422-2 · Cited by 513 · see citing works
Harnessing the potential of induced pluripotent stem cells for regenerative medicine
Wu, S. M., & Hochedlinger, K. (2011) · Nature Cell Biology · doi:10.1038/ncb0511-497 · Cited by 508 · see citing works
Reinhardt, P., Schmid, B., Burbulla, L. F., Schöndorf, D. C., Wagner, L., Glatza, M., Höing, S., Hargus, G., Heck, S. A., Dhingra, A., et al. (2013) · Cell stem cell · doi:10.1016/j.stem.2013.01.008 · Cited by 500 · see citing works
The rise of three-dimensional human brain cultures
Pașca, S. P. (2018) · Nature · doi:10.1038/nature25032 · Cited by 509 · see citing works
A TALEN Genome-Editing System for Generating Human Stem Cell-Based Disease Models
Ding, Q., Lee, Y., Schaefer, E. A. K., Peters, D., Veres, A., Kim, K. J., Kuperwasser, N., Motola, D., Meissner, T. B., Hendriks, W. T. J., et al. (2012) · Cell stem cell · doi:10.1016/j.stem.2012.11.011 · Cited by 501 · see citing works
hESC-Derived Thalamic Organoids Form Reciprocal Projections When Fused with Cortical Organoids
Xiang, Y., Tanaka, Y., Cakir, B., Patterson, B., Kim, K.-Y., Sun, P., Kang, Y.-J., Zhong, M., Liu, X., Patra, P., et al. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2018.12.015 · Cited by 485 · see citing works
A functionally characterized test set of human induced pluripotent stem cells
Boulting, G. L., Kiskinis, E., Croft, G. F., Amoroso, M. W., Oakley, D. H., Wainger, B. J., Williams, D. J., Kahler, D. J., Yamaki, M., Davidow, L. S., et al. (2011) · Nature Biotechnology · doi:10.1038/nbt.1783 · Cited by 489 · see citing works
Parkinson’s disease induced pluripotent stem cells with triplication of the α-synuclein locus
Devine, M. J., Ryten, M., Vodicka, P., Thomson, A. J., Burdon, T., Houlden, H., Cavaleri, F., Nagano, M., Drummond, N. J., Taanman, J.-W., et al. (2011) · Nature Communications · doi:10.1038/ncomms1453 · Cited by 486 · see citing works
SHANK3 and IGF1 restore synaptic deficits in neurons from 22q13 deletion syndrome patients
Shcheglovitov, A., Shcheglovitova, O., Yazawa, M., Portmann, T., Shu, R., Sebastiano, V., Krawisz, A., Froehlich, W., Bernstein, J. A., Hallmayer, J. F., et al. (2013) · Nature · doi:10.1038/nature12618 · Cited by 470 · see citing works
Pax6 is a human neuroectoderm cell fate determinant
Zhang, X., Huang, C. T., Chen, J., Pankratz, M. T., Xi, J., Li, J., Yang, Y., LaVaute, T. M., Li, X.-J., Ayala, M., et al. (2010) · Cell stem cell · doi:10.1016/j.stem.2010.04.017 · Cited by 480 · see citing works
Induced pluripotent stem cells — opportunities for disease modelling and drug discovery
Grs̆ković, M., Javaherian, A., Strulovici, B., & Daley, G. Q. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3577 · Cited by 474 · see citing works
Wang, J., Gallagher, D., DeVito, L. M., Cancino, G. I., Tsui, D., He, L., Keller, G. M., Frankland, P. W., Kaplan, D. R., & Miller, F. D. (2012) · Cell Stem Cell · doi:10.1016/j.stem.2012.03.016 · Cited by 474 · see citing works
Modeling Alzheimer’s disease with iPSC-derived brain cells
Penney, J., Ralvenius, W. T., & Tsai, L.-H. (2020) · Molecular Psychiatry · doi:10.1038/s41380-019-0468-3 · Cited by 471 · see citing works
Pluripotent stem cells in regenerative medicine: challenges and recent progress
Tabar, V. S., & Studer, L. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3563 · Cited by 458 · see citing works
Self-citationGeneration and expansion of highly pure motor neuron progenitors from human pluripotent stem cells
Du, Z., Chen, H., Liu, H., Lü, J., Qian, K. X., Huang, C., Zhong, X., Fan, F., & Zhang, S. (2015) · Nature Communications · doi:10.1038/ncomms7626 · Cited by 455 · see citing works
Induced pluripotent stem cells (iPSCs): molecular mechanisms of induction and applications
Cerneckis, J., Cai, H., & Shi, Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01809-0 · Cited by 452 · see citing works
Reinhardt, P., Glatza, M., Hemmer, K., Tsytsyura, Y., Thiel, C. S., Höing, S., Moritz, S., Parga, J. A., Wagner, L., Bruder, J. M., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0059252 · Cited by 443 · see citing works
Identification and Rescue of α-Synuclein Toxicity in Parkinson Patient–Derived Neurons
Chung, C. Y., Khurana, V., Auluck, P. K., Tardiff, D. F., Mazzulli, J. R., Soldner, F., Baru, V., Lou, Y., Freyzon, Y., Cho, S., et al. (2013) · Science · doi:10.1126/science.1245296 · Cited by 442 · see citing works
SMN2 splice modulators enhance U1–pre-mRNA association and rescue SMA mice
Palacino, J., Swalley, S. E., Song, C., Cheung, A. K., Shu, L., Zhang, X., Van Hoosear, M., Shin, Y., Chin, D. N., Keller, C. G., et al. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1837 · Cited by 432 · see citing works
Doi, D., Samata, B., Katsukawa, M., Kikuchi, T., Morizane, A., Ono, Y., Sekiguchi, K., Nakagawa, M., Parmar, M., & Takahashi, J. B. (2014) · Stem Cell Reports · doi:10.1016/j.stemcr.2014.01.013 · Cited by 434 · see citing works
Small-Molecule-Driven Direct Reprogramming of Mouse Fibroblasts into Functional Neurons.
Li, X., Zuo, X., Jing, J., Ma, Y., Wang, J., Liu, D., Zhu, J., Du, X., Xiong, L., Du, Y., et al. (2015) · Cell Stem Cell · doi:10.1016/j.stem.2015.06.003 · Cited by 428 · see citing works
Wang, C., Najm, R., Xu, Q., Jeong, D.-E., Walker, D., Balestra, M. E., Yoon, S. Y., Yuan, H., Li, G., Miller, Z. A., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0004-z · Cited by 428 · see citing works
Efficient generation of hepatocyte-like cells from human induced pluripotent stem cells
Song, Z., Cai, J., Liu, Y., Zhao, D., Yong, J., Duo, S., Song, X., Guo, Y., Zhao, Y., Qin, H., et al. (2009) · Cell Research · doi:10.1038/cr.2009.107 · Cited by 499 · see citing works
The Long Noncoding RNA RMST Interacts with SOX2 to Regulate Neurogenesis
Ng, S., Bogu, G. K., Soh, B.-S., & Stanton, L. W. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.07.017 · Cited by 413 · see citing works
Brown, J. A., Pensabene, V., Markov, D. A., Allwardt, V., Neely, M. D., Shi, M., Britt, C. M., Hoilett, O. S., Yang, Q. K., Brewer, B. M., et al. (2015) · Biomicrofluidics · doi:10.1063/1.4934713 · Cited by 414 · see citing works
Technical Challenges in Using Human Induced Pluripotent Stem Cells to Model Disease
Saha, K., & Jaenisch, R. (2009) · Cell Stem Cell · doi:10.1016/j.stem.2009.11.009 · Cited by 411 · see citing works
Generation of inner ear sensory epithelia from pluripotent stem cells in 3D culture
Koehler, K. R., Mikosz, A. M., Molosh, A. I., Patel, D., & Hashino, E. (2013) · Nature · doi:10.1038/nature12298 · Cited by 410 · see citing works
Maury, Y., Côme, J., Piskorowski, R. A., Salah‐Mohellibi, N., Chevaleyre, V., Peschanski, M., Martinat, C., & Nedelec, S. (2014) · Nature Biotechnology · doi:10.1038/nbt.3049 · Cited by 410 · see citing works
Next-generation regenerative medicine: organogenesis from stem cells in 3D culture.
Sasai, Y. (2013) · Cell Stem Cell · doi:10.1016/j.stem.2013.04.009 · Cited by 388 · see citing works
Use of human embryonic stem cells to model pediatric gliomas with H3.3K27M histone mutation
Funato, K., Major, T., Lewis, P. W., Allis, C. D., & Tabar, V. (2014) · Science · doi:10.1126/science.1253799 · Cited by 390 · see citing works
Cerebral Organoids Recapitulate Epigenomic Signatures of the Human Fetal Brain
Luo, C., Lancaster, M. A., Castanon, R., Nery, J. R., Knoblich, J. A., & Ecker, J. R. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.12.001 · Cited by 370 · see citing works
Self‐organized developmental patterning and differentiation in cerebral organoids
Renner, M., Lancaster, M. A., Bian, S., Choi, H., Ku, T., Peer, A., Chung, K., & Knoblich, J. A. (2017) · The EMBO Journal · doi:10.15252/embj.201694700 · Cited by 389 · see citing works
Chemical reprogramming of human somatic cells to pluripotent stem cells.
Guan, J., Wang, G., Wang, J., Zhang, Z., Fu, Y., Cheng, L., Meng, G., Lyu, Y., Zhu, J., Li, Y., et al. (2022) · Nature · doi:10.1038/s41586-022-04593-5 · Cited by 388 · see citing works
Generation of anterior foregut endoderm from human embryonic and induced pluripotent stem cells
Green, M. D., Chen, A. F., Nostro, M. C., D’Souza, S. L., Schaniel, C., Lemischka, I. R., Gouon–Evans, V., Keller, G. M., & Snoeck, H. W. (2011) · Nature Biotechnology · doi:10.1038/nbt.1788 · Cited by 386 · see citing works
Efficient Derivation of Purified Lung and Thyroid Progenitors from Embryonic Stem Cells
Longmire, T. A., Ikonomou, L., Hawkins, F., Christodoulou, C., Cao, Y., Jean, J. C., Kwok, L. W., Mou, H., Rajagopal, J., Shen, S. S., et al. (2012) · Cell Stem Cell · doi:10.1016/j.stem.2012.01.019 · Cited by 384 · see citing works
Yuan, S. H., Martin, J., Elia, J., Flippin, J. D., Paramban, R. I., Hefferan, M. P., Vidal, J. G., Mu, Y., Killian, R. L., Israel, M. A., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017540 · Cited by 383 · see citing works
Gouti, M., Tsakiridis, A., Wymeersch, F. J., Huang, Y., Kleinjung, J., Wilson, V. A., & Briscoe, J. (2014) · PLoS Biology · doi:10.1371/journal.pbio.1001937 · Cited by 364 · see citing works
Stem Cell Models of Human Brain Development
Kelava, I., & Lancaster, M. A. (2016) · Cell stem cell · doi:10.1016/j.stem.2016.05.022 · Cited by 372 · see citing works
Seibler, P., Graziotto, J. J., Jeong, H., Šimunović, F., Klein, C., & Krainc, D. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.4441-10.2011 · Cited by 375 · see citing works
Li, W., Sun, W., Zhang, Y., Wei, W., Ambasudhan, R., Xia, P., Talantova, M. V., Lin, T., Kim, J., Wang, X., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1014041108 · Cited by 375 · see citing works
di Domenico, A., Carola, G., Calatayud, C., Pons-Espinal, M., Muñoz, J. P., Richaud-Patin, Y., Fernandez-Carasa, I., Gut, M., Faella, A., Parameswaran, J., et al. (2019) · Stem Cell Reports · doi:10.1016/j.stemcr.2018.12.011 · Cited by 372 · see citing works
Orlova, V. V., van den Hil, F. E., Petrus-Reurer, S., Drabsch, Y., ten Dijke, P., & Mummery, C. L. (2014) · Nature Protocols · doi:10.1038/nprot.2014.102 · Cited by 365 · see citing works
Sharma, R., Khristov, V., Rising, A. C., Jha, B. S., Dejene, R., Hotaling, N. A., Li, Y., Stoddard, J., Stankewicz, C., Wan, Q., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aat5580 · Cited by 362 · see citing works
Transcription factor binding dynamics during human ES cell differentiation
Tsankov, A. M., Gu, H., Akopian, V., Ziller, M. J., Donaghey, J., Amit, I., Gnirke, A., & Meissner, A. (2015) · Nature · doi:10.1038/nature14233 · Cited by 349 · see citing works
Cervo, P. R. D. V., Romanov, R. A., Spigolon, G., Masini, D., Martín‐Montañez, E., Toledo, E. M., Manno, G. L., Feyder, M. T., Pifl, C., Ng, Y. H., et al. (2017) · Nature Biotechnology · doi:10.1038/nbt.3835 · Cited by 357 · see citing works
HSP70 chaperones RNA-free TDP-43 into anisotropic intranuclear liquid spherical shells
Yu, H., Lu, S., Gasior, K. I., Singh, D., Vazquez‐Sanchez, S., Tapia, O., Toprani, D., Beccari, M. S., Yates, J. R., Cruz, S. D., et al. (2021) · Science · doi:10.1126/science.abb4309 · Cited by 355 · see citing works
Neuromesodermal progenitors and the making of the spinal cord
Henrique, D., Abranches, E., Verrier, L., & Storey, K. G. (2015) · Development · doi:10.1242/dev.119768 · Cited by 351 · see citing works
Brain organoids for the study of human neurobiology at the interface of in vitro and in vivo
Chiaradia, I., & Lancaster, M. A. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-00730-3 · Cited by 343 · see citing works
Dysfunction of fibroblasts of extrarenal origin underlies renal fibrosis and renal anemia in mice
Asada, N., Takase, M., Nakamura, J., Oguchi, A., Asada, M., Suzuki, N., Yamamura, K., Nagoshi, N., Shibata, S., Rao, T. N., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci57301 · Cited by 348 · see citing works
Derivation of neural crest cells from human pluripotent stem cells
Lee, G., Chambers, S. M., Tomishima, M. J., & Studer, L. (2010) · Nature Protocols · doi:10.1038/nprot.2010.35 · Cited by 344 · see citing works
Self-citationImpaired intrinsic immunity to HSV-1 in human iPSC-derived TLR3-deficient CNS cells
Lafaille, F. G., Pessach, I. M., Zhang, S., Ciancanelli, M. J., Casadio, M., Abhyankar, A., Ying, S., Keros, S., Goldstein, P. A., Mostoslavsky, G., et al. (2012) · Nature · doi:10.1038/nature11583 · Cited by 341 · see citing works
Self-citationRapid, complete and large‐scale generation of post‐mitotic neurons from the human LUHMES cell line
Scholz, D., Pöltl, D., Genewsky, A. J., Weng, M. K., Waldmann, T., Schildknecht, S., & Leist, M. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07255.x · Cited by 330 · see citing works
Human pluripotent stem cell-derived neural constructs for predicting neural toxicity
Schwartz, M. P., Hou, Z., Propson, N. E., Zhang, J., Engstrom, C. J., Costa, V. S., Jiang, P., Nguyen, B. K., Bolin, J. M., Daly, W., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1516645112 · Cited by 325 · see citing works
Lei, Y.-G., & Schaffer, D. (2013) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1309408110 · Cited by 325 · see citing works
PSEN1 Mutant iPSC-Derived Model Reveals Severe Astrocyte Pathology in Alzheimer's Disease
Oksanen, M., Petersen, A. J., Naumenko, N., Puttonen, K., Lehtonen, Š., Gubert Olivé, M., Shakirzyanova, A., Leskelä, S., Sarajärvi, T., Viitanen, M., et al. (2017) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.10.016 · Cited by 332 · see citing works
Bilican, B., Serio, A., Barmada, S. J., Nishimura, A. L., Sullivan, G. J., Carrasco, M., Phatnani, H. P., Puddifoot, C. A., Story, D., Fletcher, J., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1202922109 · Cited by 328 · see citing works
Falk, A., Koch, P., Kesavan, J., Takashima, Y., Ladewig, J., Alexander, M., Wiskow, O., Tailor, J. K., Trotter, M. W. B., Pollard, S. M., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0029597 · Cited by 325 · see citing works
The transcriptional and signalling networks of pluripotency
Ng, H., & Surani, M. A. (2011) · Nature Cell Biology · doi:10.1038/ncb0511-490 · Cited by 323 · see citing works
Modeling ALS with iPSCs reveals that mutant SOD1 misregulates neurofilament balance in motor neurons
Chen, H., Qian, K., Du, Z., Cao, J., Petersen, A., Liu, H., Blackbourn, L. W., Huang, C.-L., Errigo, A., Yin, Y., et al. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.02.004 · Cited by 318 · see citing works
McCauley, H. A., & Wells, J. M. (2017) · Development · doi:10.1242/dev.140731 · Cited by 322 · see citing works
Small molecules enable highly efficient neuronal conversion of human fibroblasts.
Ladewig, J., Mertens, J., Kesavan, J., Doerr, J., Poppe, D., Glaue, F., Herms, S., Wernet, P., Kögler, G., Müller, F.-J., et al. (2012) · Nature Methods · doi:10.1038/nmeth.1972 · Cited by 316 · see citing works
Neural stem cell systems: physiological players or in vitro entities?
Conti, L., & Cattaneo, E. F. (2010) · Nature reviews. Neuroscience · doi:10.1038/nrn2761 · Cited by 319 · see citing works
Epigenetic resetting of human pluripotency
Guo, G., von Meyenn, F., Rostovskaya, M., Clarke, J., Dietmann, S., Baker, D., Sahakyan, A., Myers, S., Bertone, P., Reik, W., et al. (2017) · Development · doi:10.1242/dev.146811 · Cited by 319 · see citing works
Swistowski, A., Peng, J., Liu, Q., Mali, P., Rao, M. S., Cheng, L., & Zeng, X. (2010) · Stem Cells · doi:10.1002/stem.499 · Cited by 317 · see citing works
Dishing out mini-brains: Current progress and future prospects in brain organoid research
Kelava, I., & Lancaster, M. A. (2016) · Developmental Biology · doi:10.1016/j.ydbio.2016.06.037 · Cited by 309 · see citing works
Li, Y., Wang, H., Muffat, J., Cheng, A. W., Orlando, D. A., Lovén, J., Kwok, S., Feldman, D., Bateup, H. S., Gao, Q., et al. (2013) · Cell stem cell · doi:10.1016/j.stem.2013.09.001 · Cited by 305 · see citing works
The future of stem cell therapies for Parkinson disease
Parmar, M., Grealish, S., & Henchcliffe, C. (2020) · Nature reviews. Neuroscience · doi:10.1038/s41583-019-0257-7 · Cited by 314 · see citing works
- Authors
- Chambers, S. M., Fasano, C. A., Papapetrou, E. P., Tomishima, M., Sadelain, M., & Studer, L.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Chambers, Stuart M
- Studer, Lorenz
- Venue
- Nature Biotechnology
- Published
- 2009-03
- Volume
- 27
- Issue
- 3
- Pages
- 275-280
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC2756723
- OpenAlex
- W2087786585
- Cited by
- 3,620
- References
- 24
- Citations by year
- 2026: 155 · 2025: 211 · 2024: 225 · 2023: 241 · 2022: 229 · 2021: 287 · 2020: 292 · 2019: 238 · 2018: 241 · 2017: 235 · 2016: 240 · 2015: 225 · 2014: 185 · 2013: 199 · 2012: 184
- FWCI
- 55.89
- Type
- journal article
- Language
- en
- Update notices
- erratum (2009-05-01)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS052671)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- neuronal differentiation, human embryonic stem cells, induced pluripotent stem cells, noggin, SB431542, epiblast-like cells, Pax6, rosette formation, midbrain dopaminergic neurons, spinal motoneurons, adherent culture
- MeSH terms
- Noggin Protein, Carrier Proteins, Cell Differentiation, Humans, Mesencephalon, Neurons, Signal Transduction, Cell Culture Techniques, Pluripotent Stem Cells, Smad Proteins, Embryonic Stem Cells
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