Differentiation of spinal motor neurons from pluripotent human stem cells
Open accessAbstract
We have devised a reproducible protocol by which human embryonic stem cells (hESCs) or inducible pluripotent stem cells (iPSCs) are efficiently differentiated to functional spinal motor neurons. This protocol comprises four major steps. Pluripotent stem cells are induced to form neuroepithelial (NE) cells that form neural tube-like rosettes in the absence of morphogens in the first 2 weeks. The NE cells are then specified to OLIG2-expressing motoneuron progenitors in the presence of retinoic acid (RA) and sonic hedgehog (SHH) or purmorphamine in the next 2 weeks. These progenitor cells further generate post-mitotic, HB9-expressing motoneurons at the 5th week and mature to functional motor neurons thereafter. It typically takes 5 weeks to generate the post-mitotic motoneurons and 8-10 weeks for the production of functional mature motoneurons. In comparison with other methods, our protocol does not use feeder cells, has a minimum dependence on proteins (purmorphamine replacing SHH), has controllable adherent selection and is adaptable for scalable suspension culture.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Robust protocols exist for differentiating human ES or iPS cells into neurons, astrocytes and oligodendrocytes.
“Robust protocols have been developed to induce human ES or iPS cells to differentiate into the different neuroectodermal cell types of the CNS including neurons, astrocytes and oligodendrocytes 7,8.”
From Efficient derivation of microglia-like cells from human pluripotent stem cells (2016) · cites this paper as [8]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Ranade, V. (2009) · American Journal of Therapeutics · doi:10.1097/mjt.0b013e31817c941f · Cited by 2,790 · see citing works
In vitro differentiation of transplantable neural precursors from human embryonic stem cells
Zhang, S., Wernig, M., Duncan, I. D., Brüstle, O., & Thomson, J. A. (2001) · Nature Biotechnology · doi:10.1038/nbt1201-1129 · Cited by 1,916 · see citing works
Self-citationDirected differentiation of embryonic stem cells into motor neurons.
Wichterle, H., Lieberam, I., Porter, J. A., & Jessell, T. (2002) · Cell · doi:10.1016/s0092-8674(02)00835-8 · Cited by 1,792 · see citing works
Pax6 Controls Progenitor Cell Identity and Neuronal Fate in Response to Graded Shh Signaling
Ericson, J., Rashbass, P., Schedl, A., Brenner‐Morton, S., Kawakami, A., van Heyningen, V., Jessell, T. M., & Briscoe, J. (1997) · Cell · doi:10.1016/s0092-8674(00)80323-2 · Cited by 1,044 · 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
Lu, Q. R., Yuk, D.-I., Alberta, J., Zhu, Z.-M., Pawlitzky, I., Chan, J., McMahon, A., Stiles, C., & Rowitch, D. H. (2000) · Neuron · doi:10.1016/s0896-6273(00)80897-1 · Cited by 883 · see citing works
Roy, N. S., Cléren, C., Singh, S. K., Yang, L., Beal, M. F., & Goldman, S. A. (2006) · Nature Medicine · doi:10.1038/nm1495 · Cited by 822 · see citing works
Zhou, Q., Wang, S., & Anderson, D. J. (2000) · Neuron · doi:10.1016/s0896-6273(00)80898-3 · Cited by 789 · see citing works
Directed differentiation of telencephalic precursors from embryonic stem cells
Watanabe, K., Kamiya, D., Nishiyama, A., Katayama, T., Nozaki, S., Kawasaki, H., Watanabe, Y., Mizuseki, K., & Sasai, Y. (2005) · Nature Neuroscience · doi:10.1038/nn1402 · Cited by 784 · see citing works
Specification 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
Self-citationNistor, G. I., Totoiu, M. O., Haque, N. S. K., Carpenter, M. K., & Keirstead, H. S. (2004) · Glia · doi:10.1002/glia.20127 · Cited by 580 · see citing works
Directed Differentiation of Dopaminergic Neuronal Subtypes from Human Embryonic Stem Cells
Yan, Y., Yang, D., Żarnowska, E. D., Du, Z., Werbel, B., Valliere, C., Pearce, R. A., Thomson, J. A., & Zhang, S. (2005) · Stem Cells · doi:10.1634/stemcells.2004-0365 · Cited by 489 · see citing works
Self-citationMizuguchi, R., Sugimori, M., Takebayashi, H., Kosako, H., Nagao, M., Yoshida, S., Nabeshima, Y., Shimamura, K., & Nakafuku, M. (2001) · Neuron · doi:10.1016/s0896-6273(01)00413-5 · Cited by 471 · see citing works
Directed Differentiation of Human-Induced Pluripotent Stem Cells Generates Active Motor Neurons
Karumbayaram, S., Novitch, B. G., Patterson, M., Umbach, J. A., Richter, L., Lindgren, A., Conway, A. E., Clark, A. T., Goldman, S. A., Plath, K., et al. (2009) · Stem Cells · doi:10.1002/stem.31 · Cited by 373 · see citing works
Okada, Y., Shimazaki, T., Sobue, G., & Okano, H. (2004) · Developmental Biology · doi:10.1016/j.ydbio.2004.07.038 · Cited by 333 · see citing works
Johnson, M. A., Weick, J. P., Pearce, R. A., & Zhang, S.-C. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.4562-06.2007 · Cited by 318 · see citing works
Self-citationPankratz, M. T., Li, X.-J., LaVaute, T. M., Lyons, E. A., Chen, X., & Zhang, S. (2007) · Stem Cells · doi:10.1634/stemcells.2006-0707 · Cited by 315 · see citing works
Self-citationLi, X.-J., Hu, B., Jones, S. A., Zhang, Y., LaVaute, T. M., Du, Z., & Zhang, S. (2008) · Stem Cells · doi:10.1634/stemcells.2007-0620 · Cited by 278 · see citing works
Self-citationMizuseki, K., Sakamoto, T., Watanabe, K., Muguruma, K., Ikeya, M., Nishiyama, A., Arakawa, A., Suemori, H., Nakatsuji, N., Kawasaki, H., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1037282100 · Cited by 273 · see citing works
Martı́, E., Gibson, S. J., Polak, J. M., Facer, P., Springall, D. R., Aswegen, G. V., Aitchison, M., & Koltzenburg, M. (1987) · The Journal of Comparative Neurology · doi:10.1002/cne.902660304 · Cited by 251 · see citing works
Olig2 and Ngn2 function in opposition to modulate gene expression in motor neuron progenitor cells.Preprint
Lee, S.-K., Lee, B., Ruiz, E. C., & Pfaff, S. (2005) · Genes & Development · doi:10.1101/gad.1257105 · Cited by 226 · see citing works
Hu, B.-Y., Du, Z.-W., Li, X.-J., Ayala, M., & Zhang, S.-C. (2009) · Development · doi:10.1242/dev.029447 · Cited by 169 · see citing works
Self-citationRoy, N. S., Nakano, T., Xuing, L., Kang, J., Nedergaard, M., & Goldman, S. A. (2005) · Experimental Neurology · doi:10.1016/j.expneurol.2005.06.021 · Cited by 148 · see citing works
Neural Subtype Specification from Embryonic Stem Cells
Zhang, S. (2006) · Brain Pathology · doi:10.1111/j.1750-3639.2006.00008.x · Cited by 140 · see citing works
Self-citationOlig Transcription Factors Are Expressed in Oligodendrocyte and Neuronal Cells in Human Fetal CNS
Jakovcevski, I., & Zečević, N. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.2324-05.2005 · Cited by 130 · see citing works
Regulation of Neural Specification from Human Embryonic Stem Cells by BMP and FGF
LaVaute, T. M., Yoo, Y. D., Pankratz, M. T., Weick, J. P., Gerstner, J. R., & Zhang, S. (2009) · Stem Cells · doi:10.1002/stem.99 · Cited by 92 · see citing works
Self-citationDifferentiation of Neuroepithelia from Human Embryonic Stem Cells
Xia, X., & Zhang, S. (2009) · Methods in molecular biology · doi:10.1007/978-1-60327-931-4_4 · Cited by 36 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
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
Self-citationEfficient derivation of microglia-like cells from human pluripotent stem cells
Muffat, J., Li, Y., Yuan, B., Mitalipova, M., Omer, A., Corcoran, S., Bakiasi, G., Tsai, L.-H., Aubourg, P., Ransohoff, R. M., et al. (2016) · Nature Medicine · doi:10.1038/nm.4189 · Cited by 651 · 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
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
Specification of transplantable astroglial subtypes from human pluripotent stem cells
Krencik, R., Weick, J. P., Liu, Y., Zhang, Z., & Zhang, S. (2011) · Nature Biotechnology · doi:10.1038/nbt.1877 · Cited by 401 · see citing works
Self-citationSpinal cord reconstitution with homologous neural grafts enables robust corticospinal regeneration
Kadoya, K., Lu, P., Nguyen, K., Lee-Kubli, C. A., Kumamaru, H., Yao, L., Knackert, J. A., Poplawski, G. H. D., Dulin, J. N., Strobl, H., et al. (2016) · Nature Medicine · doi:10.1038/nm.4066 · Cited by 396 · see citing works
Self-citationLei, 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
Directed differentiation of forebrain GABA interneurons from human pluripotent stem cells
Liu, Y., Liu, H., Sauvey, C., Yao, L., Żarnowska, E. D., & Zhang, S. (2013) · Nature Protocols · doi:10.1038/nprot.2013.106 · Cited by 300 · see citing works
Self-citationDirected differentiation of functional astroglial subtypes from human pluripotent stem cells
Krencik, R., & Zhang, S. (2011) · Nature Protocols · doi:10.1038/nprot.2011.405 · Cited by 300 · see citing works
Self-citationTransplanting neural progenitor cells to restore connectivity after spinal cord injury
Fischer, I., Dulin, J. N., & Lane, M. A. (2020) · Nature reviews. Neuroscience · doi:10.1038/s41583-020-0314-2 · Cited by 297 · see citing works
Modeling ALS with motor neurons derived from human induced pluripotent stem cells
Sances, S., Bruijn, L. I., Chandran, S., Eggan, K., Ho, R., Klim, J. R., Livesey, M. R., Lowry, E., Macklis, J. D., Rushton, D., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4273 · Cited by 289 · see citing works
Self-citationLiu, Y., Weick, J. P., Liu, H., Krencik, R., Zhang, X., Ma, L., Zhou, G., Ayala, M., & Zhang, S. (2013) · Nature Biotechnology · doi:10.1038/nbt.2565 · Cited by 276 · see citing works
Self-citationDifferentiation of human oligodendrocytes from pluripotent stem cells
Hu, B., Du, Z., & Zhang, S. (2009) · Nature Protocols · doi:10.1038/nprot.2009.186 · Cited by 260 · see citing works
Self-citationNolbrant, S., Heuer, A., Parmar, M., & Kirkeby, A. (2017) · Nature Protocols · doi:10.1038/nprot.2017.078 · Cited by 252 · see citing works
Accelerated High-Yield Generation of Limb-Innervating Motor Neurons from Human Stem Cells
Amoroso, M. W., Croft, G. F., Williams, D. J., O’Keeffe, S., Carrasco, M. A., Davis, A. R., Roybon, L., Oakley, D. H., Maniatis, T., Henderson, C. E., et al. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.0906-12.2013 · Cited by 244 · see citing works
Dafinca, R., Scaber, J., Ababneh, N. A., Lalic, T., Weir, G. A., Christian, H., Vowles, J., Douglas, A. G. L., Fletcher-Jones, A., Browne, C., et al. (2016) · Stem Cells · doi:10.1002/stem.2388 · Cited by 234 · see citing works
Cooper, O., Hargus, G., Deleidi, M., Blak, A. A., Osborn, T. M., Marlow, E. D., Lee, K., Levy, A. E., Perez-Torres, E., Yow, A., et al. (2010) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2010.06.017 · Cited by 227 · see citing works
Ahuja, C. S., & Fehlings, M. G. (2016) · Stem Cells Translational Medicine · doi:10.5966/sctm.2015-0381 · Cited by 219 · see citing works
Corti, S. P., Nizzardo, M., Simone, C., Falcone, M., Nardini, M., Ronchi, D., Donadoni, C., Salani, S., Riboldi, G. M., Magri, F., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004108 · Cited by 205 · see citing works
Zeng, H., Guo, M., Martins‐Taylor, K., Wang, X., Zhang, Z., Park, J. W., Zhan, S., Kronenberg, M. S., Lichtler, A. C., Liu, H.-X., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011853 · Cited by 196 · see citing works
Hester, M. E., Murtha, M. J., Song, S., Rao, M., Miranda, C. J., Meyer, K., Tian, J., Boulting, G., Schaffer, D. V., Zhu, M. X., et al. (2011) · Molecular Therapy · doi:10.1038/mt.2011.135 · Cited by 183 · see citing works
Constructing and Deconstructing Stem Cell Models of Neurological Disease
Han, S. S. W., Williams, L. A., & Eggan, K. C. (2011) · Neuron · doi:10.1016/j.neuron.2011.05.003 · Cited by 159 · see citing works
Aoki, Y., Manzano, R., Lee, Y., Dafinca, R., Aoki, M., Douglas, A. G. L., Varela, M. A., Sathyaprakash, C., Scaber, J., Barbagallo, P., et al. (2017) · Brain · doi:10.1093/brain/awx024 · Cited by 159 · see citing works
Xu, Y., Qiu, Y., Zhang, B., Chen, G., Chen, Q., Wang, M., Mo, F., Xu, J., Wu, J., Zhang, R., et al. (2019) · Cell Research · doi:10.1038/s41422-019-0152-9 · Cited by 157 · see citing works
Self-citationInduced Pluripotent Stem Cells for Regenerative Medicine
Hirschi, K. K., Li, S., & Roy, K. (2014) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-071813-105108 · Cited by 149 · see citing works
Qu, Q., Li, D., Louis, K. R., Li, X., Yang, H. B., Sun, Q., Crandall, S. R., Tsang, S., Zhou, J., Cox, C. L., et al. (2014) · Nature Communications · doi:10.1038/ncomms4449 · Cited by 147 · see citing works
High-throughput compound evaluation on 3D networks of neurons and glia in a microfluidic platform
Wevers, N. R., van Vught, R., Wilschut, K. J., Nicolas, A., Chiang, C., Lanz, H. L., Trietsch, S. J., Joore, J., & Vulto, P. (2016) · Scientific Reports · doi:10.1038/srep38856 · Cited by 147 · see citing works
Specification of neuronal and glial subtypes from human pluripotent stem cells
Liu, H., & Zhang, S. (2011) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-011-0770-y · Cited by 142 · see citing works
Self-citationHow to make spinal motor neurons
Davis‐Dusenbery, B. N., Williams, L. A., Klim, J. R., & Eggan, K. C. (2014) · Development · doi:10.1242/dev.097410 · Cited by 137 · see citing works
Binan, L., Tendey, C., Crescenzo, G. D., El‐Ayoubi, R., Ajji, A., & Jolicœur, M. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.09.097 · Cited by 138 · see citing works
Progress in Stem Cell Therapy for Major Human Neurological Disorders
Martínez‐Morales, P., Revilla, A., Ocaña, I., González, C., Sainz, P., McGuire, D., & Liste, I. (2013) · Stem Cell Reviews and Reports · doi:10.1007/s12015-013-9443-6 · Cited by 127 · see citing works
Picchiarelli, G., Demestre, M., Zuko, A., Been, M., Higelin, J., Dieterle, S., Goy, M.-A., Mallik, M., Sellier, C., Scekic‐Zahirovic, J., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0498-9 · Cited by 127 · see citing works
Lippmann, E. S., Estevez-Silva, M. C., & Ashton, R. S. (2013) · Stem Cells · doi:10.1002/stem.1622 · Cited by 123 · see citing works
Fong, H., Wang, C., Knoferle, J., Walker, D., Balestra, M. E., Tong, L. M., Leung, L., Ring, K. L., Seeley, W. W., Karydas, A., et al. (2013) · Stem Cell Reports · doi:10.1016/j.stemcr.2013.08.001 · Cited by 122 · see citing works
Biological and medical applications of a brain-on-a-chip
Pamies, D., Härtung, T., & Högberg, H. T. (2014) · Experimental Biology and Medicine · doi:10.1177/1535370214537738 · Cited by 117 · see citing works
Induced pluripotent stem cells: a new revolution for clinical neurology?
Mattis, V. B., & Svendsen, C. N. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(11)70022-9 · Cited by 112 · see citing works
Comparison and Optimization of hiPSC Forebrain Cortical Differentiation Protocols
Muratore, C., Srikanth, P., Callahan, D. G., & Young‐Pearse, T. L. (2014) · PLoS ONE · doi:10.1371/journal.pone.0105807 · Cited by 113 · see citing works
Mahairaki, V., Lim, S. H., Christopherson, G. T., Xu, L., Nasonkin, I. O., Yu, C. K., Mao, H., & Koliatsos, V. E. (2010) · Tissue Engineering Part A · doi:10.1089/ten.tea.2010.0377 · Cited by 112 · see citing works
Nizzardo, M., Simone, C., Rizzo, F., Ruggieri, M., Salani, S., Riboldi, G. M., Faravelli, I., Zanetta, C., Bresolin, N., Comi, G. P., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt425 · Cited by 112 · see citing works
Peng, L., Liu, H., Ruan, H., Tepp, W. H., Stoothoff, W. H., Brown, R. H., Johnson, E. A., Yao, W., Zhang, S., & Dong, M. (2013) · Nature Communications · doi:10.1038/ncomms2462 · Cited by 108 · see citing works
Self-citationTERT activation targets DNA methylation and multiple aging hallmarks
Shim, H. S., Iaconelli, J., Shang, X., Li, J., Lan, Z. D., Jiang, S., Nutsch, K., Beyer, B. A., Lairson, L. L., Boutin, A. T., et al. (2024) · Cell · doi:10.1016/j.cell.2024.05.048 · Cited by 104 · see citing works
Giacomelli, E., Vahsen, B. F., Calder, E. L., Xu, Y., Scaber, J., Gray, E., Dafinca, R., Talbot, K., & Studer, L. (2022) · Cell stem cell · doi:10.1016/j.stem.2021.12.008 · Cited by 97 · see citing works
Gao, S., Guo, X., Zhao, S., Jin, Y., Zhou, F., Yuan, P., Cao, L., Wang, J., Qiu, Y., Sun, C., et al. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1772-1 · Cited by 100 · see citing works
Differential neuronal vulnerability identifies IGF-2 as a protective factor in ALS
Allodi, I., Comley, L. H., Nichterwitz, S., Nizzardo, M., Simone, C., Benitez, J. A., Cao, M., Corti, S. P., & Hedlund, E. (2016) · Scientific Reports · doi:10.1038/srep25960 · Cited by 96 · see citing works
Rigamonti, A., Repetti, G. G., Sun, C., Price, F. D., Larrow, D. R., Rapino, F. A., Weisinger, K., Benkler, C., Peterson, Q. P., Davidow, L. S., et al. (2016) · Stem Cell Reports · doi:10.1016/j.stemcr.2016.05.010 · Cited by 94 · see citing works
Demestre, M., Orth, M., Föhr, K. J., Achberger, K., Ludolph, A. C., Liebau, S., & Boeckers, T. M. (2015) · Stem Cell Research · doi:10.1016/j.scr.2015.07.005 · Cited by 95 · see citing works
Nutt, S. E., Chang, E.-A., Suhr, S. T., Schlosser, L. O., Mondello, S. E., Moritz, C. T., Cibelli, J. B., & Horner, P. J. (2013) · Experimental Neurology · doi:10.1016/j.expneurol.2013.07.010 · Cited by 93 · see citing works
Ichiyanagi, N., Fujimori, K., Yano, M., Ishihara-Fujisaki, C., Sone, T., Akiyama, T., Okada, Y., Akamatsu, W., Matsumoto, T., Ishikawa, M., et al. (2016) · Stem Cell Reports · doi:10.1016/j.stemcr.2016.02.011 · Cited by 93 · see citing works
DNAJB6, a Key Factor in Neuronal Sensitivity to Amyloidogenesis
Thiruvalluvan, A., de Mattos, E. P., Brunsting, J. F., Bakels, R., Serlidaki, D., Barazzuol, L., Conforti, P., Fatima, A., Koyuncu, S., Cattaneo, E. F., et al. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.02.022 · Cited by 88 · see citing works
Li, L., Chao, J., & Shi, Y. (2018) · Cell and Tissue Research · doi:10.1007/s00441-017-2713-x · Cited by 89 · see citing works
Stacpoole, S. R. L., Spitzer, S., Bilican, B., Compston, A., Káradóttir, R., Chandran, S., & Franklin, R. (2013) · Stem Cell Reports · doi:10.1016/j.stemcr.2013.09.006 · Cited by 88 · see citing works
Muratore, C., Zhou, C. Q., Liao, M., Fernandez, M. A., Taylor, W. M., Lagomarsino, V. N., Pearse, R. V., Rice, H. C., Negri, J. M., He, A., et al. (2017) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.10.015 · Cited by 82 · see citing works
NEK1 loss-of-function mutation induces DNA damage accumulation in ALS patient-derived motoneurons
Higelin, J., Catanese, A., Semelink-Sedlacek, L. L., Oeztuerk, S., Lutz, A.-K., Bausinger, J., Barbi, G., Speit, G., Andersen, P. M., Ludolph, A. C., et al. (2018) · Stem Cell Research · doi:10.1016/j.scr.2018.06.005 · Cited by 84 · see citing works
Haston, K. M., & Finkbeiner, S. M. (2015) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010715-103548 · Cited by 81 · see citing works
Raitano, S., Ordovás, L., Muynck, L. D., Guo, W., Espuny-Camacho, I., Geraerts, M., Khurana, S., Vanuytsel, K., Tóth, B. I., Voets, T., et al. (2014) · Stem Cell Reports · doi:10.1016/j.stemcr.2014.12.001 · Cited by 82 · see citing works
Higelin, J., Demestre, M., Putz, S., Delling, J. P., Jacob, C., Lutz, A.-K., Bausinger, J., Huber, A., Klingenstein, M., Barbi, G., et al. (2016) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2016.00290 · Cited by 82 · see citing works
Pouya, A., Satarian, L., Kiani, S., Javan, M., & Baharvand, H. (2011) · PLoS ONE · doi:10.1371/journal.pone.0027925 · Cited by 80 · see citing works
Regulation of ECM degradation and axon guidance by growth cone invadosomes
Santiago‐Medina, M., Gregus, K. A., Nichol, R. H., O'Toole, S. M., & Gómez, T. M. (2015) · Development · doi:10.1242/dev.108266 · Cited by 80 · see citing works
la Vega, L. D., Gómez, D. A. R., Abelseth, E., Abelseth, L., da Silva, V. A., & Willerth, S. M. (2018) · Applied Sciences · doi:10.3390/app8122414 · Cited by 79 · see citing works
Mohamad, O., Drury-Stewart, D., Song, M., Ben, F., Chen, D., Yu, S. P., & Wei, L. (2013) · PLoS ONE · doi:10.1371/journal.pone.0064160 · Cited by 80 · see citing works
Directed Differentiation of Neural-stem cells and Subtype-Specific Neurons from hESCs
Hu, B., & Zhang, S. (2010) · Methods in molecular biology · doi:10.1007/978-1-60761-691-7_8 · Cited by 77 · see citing works
Self-citationToward a 3D model of human brain development for studying gene/environment interactions
Högberg, H. T., Bressler, J. P., Christian, K. M., Harris, G., Makri, G., O’Driscoll, C. M., Pamies, D., Smirnova, L., Wen, Z., & Härtung, T. (2013) · Stem Cell Research & Therapy · doi:10.1186/scrt365 · Cited by 76 · see citing works
Extracellular matrix and biomimetic engineering microenvironment for neuronal differentiation
Yim, E. K. F., Jain, D., Mattiassi, S., & Goh, E. K. (2019) · Neural Regeneration Research · doi:10.4103/1673-5374.266907 · Cited by 76 · see citing works
Shim, H. S., Horner, J. W., Wu, C.-J., Li, J., Lan, Z. D., Jiang, S., Xu, X., Hsu, W.-H., Zal, T., Flores, I. I., et al. (2021) · Nature Aging · doi:10.1038/s43587-021-00146-z · Cited by 73 · see citing works
Autism-associated SHANK3 mutations impair maturation of neuromuscular junctions and striated muscles
Lutz, A.-K., Pfaender, S., Incearap, B., Ioannidis, V., Ottonelli, I., Föhr, K. J., Cammerer, J., Zoller, M., Higelin, J., Giona, F., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aaz3267 · Cited by 73 · see citing works
Stem Cell Technology for the Study and Treatment of Motor Neuron Diseases
Lunn, J. S., Sakowski, S. A., Federici, T., Glass, J. D., Boulis, N. M., & Feldman, E. L. (2011) · Regenerative Medicine · doi:10.2217/rme.11.6 · Cited by 71 · see citing works
Bhinge, A., Namboori, S. C., Bithell, A., Soldati, C., Buckley, N. J., & Stanton, L. W. (2015) · Stem Cells · doi:10.1002/stem.2233 · Cited by 69 · see citing works
Alves, C. J., Dariolli, R., Jorge, F. M. H., Monteiro, M. R., Maximino, J. R., Martins, R. S., Strauss, B. E., Krieger, J. E., Callegaro, D., & Chadi, G. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00289 · Cited by 70 · see citing works
Moya, N., Cutts, J., Gaasterland, T., Willert, K., & Brafman, D. A. (2014) · Stem Cell Reports · doi:10.1016/j.stemcr.2014.10.004 · Cited by 67 · see citing works
Human motor neuron generation from embryonic stem cells and induced pluripotent stem cells
Nizzardo, M., Simoné, C., Falcone, M., Locatelli, F., Riboldi, G. M., Comi, G. P., & Corti, S. P. (2010) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-010-0463-y · Cited by 69 · see citing works
Directed differentiation of basal forebrain cholinergic neurons from human pluripotent stem cells
Hu, Y. F., Qu, Z.-Y., Cao, S.-Y., Li, Q., Ma, L., Krencik, R., Xu, M., & Liu, Y. (2016) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2016.03.017 · Cited by 69 · see citing works
Engineering the human pluripotent stem cell microenvironment to direct cell fate
Hazeltine, L. B., Selekman, J. A., & Palecek, S. P. (2013) · Biotechnology Advances · doi:10.1016/j.biotechadv.2013.03.002 · Cited by 66 · see citing works
Chan, L. Y., Birch, W. R., Yim, E. K. F., & Choo, A. B. H. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2012.09.033 · Cited by 67 · see citing works
Rizzo, F., Ronchi, D., Salani, S., Nizzardo, M., Fortunato, F., Bordoni, A., Stuppia, G., Bo, R. D., Piga, D., Fato, R., et al. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw258 · Cited by 64 · see citing works
Human induced pluripotent stem cell-derived beating cardiac tissues on paper
Wang, L., Xu, C., Zhu, Y., Yu, Y., Sun, N., Zhang, X., Feng, K., & Qin, J. (2015) · Lab on a Chip · doi:10.1039/c5lc00919g · Cited by 61 · see citing works
Spinal muscular atrophy patient-derived motor neurons exhibit hyperexcitability
Liu, H., Lü, J., Chen, H., Du, Z., Li, X.-J., & Zhang, S. (2015) · Scientific Reports · doi:10.1038/srep12189 · Cited by 60 · see citing works
Self-citationEngineered Paper‐Based Cell Culture Platforms
Lantigua, D., Kelly, Y. N., Ünal, B., & Camci‐Unal, G. (2017) · Advanced Healthcare Materials · doi:10.1002/adhm.201700619 · Cited by 63 · see citing works
Current Advances and Limitations in Modeling ALS/FTD in a Dish Using Induced Pluripotent Stem Cells
Guo, W., Fumagalli, L., Prior, R. C., & Bosch, L. V. D. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00671 · Cited by 59 · see citing works
Faravelli, I., Bucchia, M., Rinchetti, P., Nizzardo, M., Simone, C., Frattini, E., & Corti, S. P. (2014) · Stem Cell Research & Therapy · doi:10.1186/scrt476 · Cited by 61 · see citing works
iPS cell derived neuronal cells for drug discovery
Heilker, R., Traub, S., Reinhardt, P., Schöler, H. R., & Sterneckert, J. L. (2014) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2014.07.003 · Cited by 60 · see citing works
Li, Y. (2014) · World Journal of Stem Cells · doi:10.4252/wjsc.v6.i1.11 · Cited by 59 · see citing works
MiR‐135b is a direct PAX6 target and specifies human neuroectoderm by inhibiting TGF‐β/BMP signaling
Bhinge, A., Poschmann, J., Namboori, S. C., Tian, X., Loh, S. J. H., Traczyk, A., Prabhakar, S., & Stanton, L. W. (2014) · The EMBO Journal · doi:10.1002/embj.201387215 · Cited by 58 · see citing works
Srikanth, P., & Young‐Pearse, T. L. (2014) · Journal of Neurogenetics · doi:10.3109/01677063.2014.881358 · Cited by 56 · see citing works
Pfaender, S., Föhr, K. J., Lutz, A.-K., Putz, S., Achberger, K., Linta, L., Liebau, S., Boeckers, T. M., & Grabrucker, A. M. (2016) · Neural Plasticity · doi:10.1155/2016/3760702 · Cited by 57 · see citing works
Stacpoole, S., Bilican, B., Webber, D. J., Luzhynskaya, A., He, X., Compston, A., Káradóttir, R. T., Franklin, R. J. M., & Chandran, S. (2011) · Nature Protocols · doi:10.1038/nprot.2011.380 · Cited by 56 · see citing works
Retinoid signaling in control of progenitor cell differentiation during mouse development
Duester, G. (2013) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2013.08.001 · Cited by 56 · see citing works
Autologous bone marrow-derived stem cells in amyotrophic lateral sclerosis
Prabhakar, S. K., Marwaha, N., Lal, V., Sharma, R. R., Rajan, R., & Khandelwal, N. (2012) · Neurology India · doi:10.4103/0028-3886.103185 · Cited by 55 · see citing works
Concise Review: Human Pluripotent Stem Cells in the Treatment of Spinal Cord Injury
Lukovic, D., Moreno‐Manzano, V., Stojković, M., Bhattacharya, S. S., & Erceg, S. (2012) · Stem Cells · doi:10.1002/stem.1159 · Cited by 55 · see citing works
Xu, L., Ryu, J., Hiel, H., Menon, A., Aggarwal, A., Rha, E. Y., Mahairaki, V., Cummings, B. J., & Koliatsos, V. E. (2015) · Stem Cell Research & Therapy · doi:10.1186/s13287-015-0087-0 · Cited by 55 · see citing works
Toma, J. S., Shettar, B., Chipman, P. H., Pinto, D. M., Borowska, J. P., Ichida, J. K., Fawcett, J. P., Zhang, Y., Eggan, K. C., & Rafuse, V. F. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.2126-14.2015 · Cited by 54 · see citing works
Montgomery, A., Wong, A., Gabers, N., & Willerth, S. M. (2014) · Biomaterials Science · doi:10.1039/c4bm00299g · Cited by 54 · see citing works
Gaspard, N., & Vanderhaeghen, P. (2010) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.2010.03827.x · Cited by 54 · see citing works
Hayashi, K., Hashimoto, M., Koda, M., Naito, A. T., Murata, A., Okawa, A., Takahashi, K., & Yamazaki, M. (2011) · Journal of Neurosurgery Spine · doi:10.3171/2011.7.spine10775 · Cited by 52 · see citing works
Accelerating neuronal aging in in vitro model brain disorders: a focus on reactive oxygen species
Campos, P. B., Paulsen, B. S., & Rehen, S. K. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00292 · Cited by 52 · see citing works
Liu, Y., Jiang, P., & Deng, W. (2011) · Nature Protocols · doi:10.1038/nprot.2011.310 · Cited by 54 · see citing works
Adams, K. L., Rousso, D. L., Umbach, J. A., & Novitch, B. G. (2015) · Nature Communications · doi:10.1038/ncomms7778 · Cited by 50 · see citing works
Steward, M., Sridhar, A., & Meyer, J. S. (2012) · Current topics in microbiology and immunology · doi:10.1007/82_2012_302 · Cited by 50 · see citing works
Generation of Functional Neuromuscular Junctions from Human Pluripotent Stem Cell Lines
Puttonen, K. A., Ruponen, M., Naumenko, N. V., Hovatta, O. H., Tavi, P., & Koıstınaho, J. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00473 · Cited by 49 · see citing works
Bayer, H., Lang, K., Buck, E., Higelin, J., Barteczko, L., Pasquarelli, N., Sprissler, J., Lucas, T., Holzmann, K., Demestre, M., et al. (2016) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.11.001 · Cited by 49 · see citing works
Current status and future prospects of stem cell therapy in Alzheimer’s disease
Fu, X., Zeng, L., Zhang, F., Jiang, J., Zhang, J.-T., & Niu, H. (2019) · Neural Regeneration Research · doi:10.4103/1673-5374.265544 · Cited by 50 · see citing works
- Authors
- Hu, B.-Y., & Zhang, S.-C.
- Affiliations
- WiCell (US)
- Corresponding author
- Zhang, Su-Chun
- ORCID
- Zhang, Su-Chun
- Venue
- Nature Protocols
- Published
- 2009-08-20
- Volume
- 4
- Issue
- 9
- Pages
- 1295-1304
- ISSN
- 1750-2799 (ISSN-L)
- 1754-2189
- PMC
- PMC2789120
- OpenAlex
- W2093994917
- Cited by
- 298
- References
- 27
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 8 · 2023: 8 · 2022: 12 · 2021: 18 · 2020: 17 · 2019: 16 · 2018: 19 · 2017: 18 · 2016: 25 · 2015: 32 · 2014: 28 · 2013: 26 · 2012: 20
- FWCI
- 7.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Protocols (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- ALS Association
- Waisman Center
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (NS 045926, NS057778, P01NS057778, R01NS045926)
- National Institute of Child Health and Human Development
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD003352)
- 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
- spinal motoneurons, human embryonic stem cells, induced pluripotent stem cells, neuronal differentiation, neuroepithelial cells, Olig2, retinoic acid, Sonic hedgehog, purmorphamine, HB9, feeder-free culture, suspension culture
- MeSH terms
- Animals, Cell Differentiation, Humans, Motor Neurons, Spinal Nerves, Time Factors, Cell Culture Techniques, Pluripotent Stem Cells, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
