Skip to main content

Advertisement

Log in

Developmental and Functional Nature of Human iPSC Derived Motoneurons

  • Published:
Stem Cell Reviews and Reports Aims and scope Submit manuscript

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

References

  1. Brookhart, J. M. (1952). A study of corticospinal activation of motor neurons. Research Publications—Association for Research in Nervous and Mental Disease, 30, 157–173.

    PubMed  CAS  Google Scholar 

  2. Dupuis, L., Gonzalez de Aguilar, J. L., Echaniz-Laguna, A., Eschbach, J., Rene, F., Oudart, H., et al. (2009). Muscle mitochondrial uncoupling dismantles neuromuscular junction and triggers distal degeneration of motor neurons. PLoS One, 4(4), e5390. doi:10.1371/journal.pone.0005390.

    Article  PubMed  Google Scholar 

  3. Dupuis, L., & Loeffler, J. P. (2009). Neuromuscular junction destruction during amyotrophic lateral sclerosis: Insights from transgenic models. Current Opinion in Pharmacology, 9(3), 341–346. doi:10.1016/j.coph.2009.03.007.

    Article  PubMed  CAS  Google Scholar 

  4. Hamburger, V. (1975). Cell death in the development of the lateral motor column of the chick embryo. The Journal of Comparative Neurology, 160(4), 535–546. doi:10.1002/cne.901600408.

    Article  PubMed  CAS  Google Scholar 

  5. Evans, M. J., & Kaufman, M. H. (1981). Establishment in culture of pluripotential cells from mouse embryos. Nature, 292(5819), 154–156.

    Article  PubMed  CAS  Google Scholar 

  6. Thomson, J. A., Itskovitz-Eldor, J., Shapiro, S. S., Waknitz, M. A., Swiergiel, J. J., Marshall, V. S., et al. (1998). Embryonic stem cell lines derived from human blastocysts. Science, 282(5391), 1145–1147.

    Article  PubMed  CAS  Google Scholar 

  7. Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126(4), 663–676.

    Article  PubMed  CAS  Google Scholar 

  8. Brennand, K. J., Simone, A., Jou, J., Gelboin-Burkhart, C., Tran, N., Sangar, S., et al. (2011). Modelling schizophrenia using human induced pluripotent stem cells. Nature, 473(7346), 221–225. doi:10.1038/nature09915.

    Article  PubMed  CAS  Google Scholar 

  9. Walsh, R. M., & Hochedlinger, K. (2010). Modeling Rett syndrome with stem cells. Cell, 143(4), 499–500. doi:10.1016/j.cell.2010.10.037.

    Article  PubMed  CAS  Google Scholar 

  10. Grabrucker, A., Vaida, B., Bockmann, J., & Boeckers, T. M. (2009). Synaptogenesis of hippocampal neurons in primary cell culture. Cell and Tissue Research, 338(3), 333–341. doi:10.1007/s00441-009-0881-z.

    Article  PubMed  Google Scholar 

  11. Kawaguchi, A., Ikawa, T., Kasukawa, T., Ueda, H. R., Kurimoto, K., Saitou, M., et al. (2008). Single-cell gene profiling defines differential progenitor subclasses in mammalian neurogenesis. Development, 135(18), 3113–3124. doi:10.1242/dev.022616.

    Article  PubMed  CAS  Google Scholar 

  12. Liebau, S., Vaida, B., Storch, A., & Boeckers, T. M. (2007). Maturation of synaptic contacts in differentiating neural stem cells. Stem Cells, 25(7), 1720–1729.

    Article  PubMed  CAS  Google Scholar 

  13. Walther, P., Wang, L., Liessem, S., & Frascaroli, G. (2010). Viral infection of cells in culture–approaches for electron microscopy. Methods in Cell Biology, 96, 603–618. doi:10.1016/S0091-679X(10)96025-1.

    Article  PubMed  Google Scholar 

  14. Baron, M. K., Boeckers, T. M., Vaida, B., Faham, S., Gingery, M., Sawaya, M. R., et al. (2006). An architectural framework that may lie at the core of the postsynaptic density. Science, 311(5760), 531–535. doi:10.1126/science.1118995.

    Article  PubMed  CAS  Google Scholar 

  15. Dale, H. H., Feldberg, W., & Vogt, M. (1936). Release of acetylcholine at voluntary motor nerve endings. The Journal of Physiology, 86(4), 353–380.

    PubMed  CAS  Google Scholar 

  16. Wu, H., Xiong, W. C., & Mei, L. (2010). To build a synapse: Signaling pathways in neuromuscular junction assembly. Development, 137(7), 1017–1033. doi:10.1242/dev.038711.

    Article  PubMed  CAS  Google Scholar 

  17. Sanes, J. R., Marshall, L. M., & McMahan, U. J. (1978). Reinnervation of muscle fiber basal lamina after removal of myofibers. Differentiation of regenerating axons at original synaptic sites. Journal of Cell Biology, 78(1), 176–198.

    Article  PubMed  CAS  Google Scholar 

  18. Witzemann, V. (2006). Development of the neuromuscular junction. Cell and Tissue Research, 326(2), 263–271. doi:10.1007/s00441-006-0237-x.

    Article  PubMed  Google Scholar 

  19. Aasen, T., Raya, A., Barrero, M. J., Garreta, E., Consiglio, A., Gonzalez, F., et al. (2008). Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes. Nature Biotechnology, 26(11), 1276–1284. doi:10.1038/nbt.1503.

    Article  PubMed  CAS  Google Scholar 

  20. Linta, L., Stockmann, M. C., Kleinhans, K. N., Boeckers, A., Storch, A., Zaehres, H., et al. (2011). Rat embryonic fibroblasts improve reprogramming of human keratinocytes into induced pluripotent stem cells. Stem Cells and Development. doi:10.1089/scd.2011.0026.

  21. Hu, B. Y., & Zhang, S. C. (2009). Differentiation of spinal motor neurons from pluripotent human stem cells. Nature Protocols, 4(9), 1295–1304. doi:10.1038/nprot.2009.127.

    Article  PubMed  CAS  Google Scholar 

  22. Bischoff, R., & Heintz, C. (1994). Enhancement of skeletal muscle regeneration. Developmental Dynamics, 201(1), 41–54.

    Article  PubMed  CAS  Google Scholar 

  23. Kleger, A., Seufferlein, T., Malan, D., Tischendorf, M., Storch, A., Wolheim, A., et al. (2010). Modulation of calcium-activated potassium channels induces cardiogenesis of pluripotent stem cells and enrichment of pacemaker-like cells. Circulation, 122(18), 1823–1836. doi:10.1161/CIRCULATIONAHA.110.971721.

    Article  PubMed  CAS  Google Scholar 

  24. Liebau, S., Steinestel, J., Linta, L., Kleger, A., Storch, A., Schoen, M., et al. (2011). An SK3 Channel/nWASP/Abi-1 complex is involved in early neurogenesis. PLoS One, 6(3), e18148. doi:10.1371/journal.pone.0018148.

    Article  PubMed  CAS  Google Scholar 

  25. Liebau, S., Vaida, B., Proepper, C., Grissmer, S., Storch, A., Boeckers, T. M., et al. (2007). Formation of cellular projections in neural progenitor cells depends on SK3 channel activity. Journal of Neurochemistry, 101(5), 1338–1350. doi:10.1111/j.1471-4159.2006.04437.x.

    Article  PubMed  CAS  Google Scholar 

  26. Ludolph, A. G., Udvardi, P. T., Schaz, U., Henes, C., Adolph, O., Weigt, H. U., et al. (2010). Atomoxetine acts as an NMDA receptor blocker in clinically relevant concentrations. British Journal of Pharmacology, 160(2), 283–291. doi:10.1111/j.1476-5381.2010.00707.x.

    Article  PubMed  CAS  Google Scholar 

  27. Li, X. J., Du, Z. W., Zarnowska, E. D., Pankratz, M., Hansen, L. O., Pearce, R. A., et al. (2005). Specification of motoneurons from human embryonic stem cells. Nature Biotechnology, 23(2), 215–221. doi:10.1038/nbt1063.

    Article  PubMed  Google Scholar 

  28. Somers, A., Jean, J. C., Sommer, C. A., Omari, A., Ford, C. C., Mills, J. A., et al. (2010). Generation of transgene-free lung disease-specific human induced pluripotent stem cells using a single excisable lentiviral stem cell cassette. Stem Cells, 28(10), 1728–1740. doi:10.1002/stem.495.

    Article  PubMed  CAS  Google Scholar 

  29. de Castro, B. M., De Jaeger, X., Martins-Silva, C., Lima, R. D., Amaral, E., Menezes, C., et al. (2009). The vesicular acetylcholine transporter is required for neuromuscular development and function. Molecular and Cellular Biology, 29(19), 5238–5250. doi:10.1128/MCB.00245-09.

    Article  PubMed  Google Scholar 

  30. Weihe, E., Tao-Cheng, J. H., Schafer, M. K., Erickson, J. D., & Eiden, L. E. (1996). Visualization of the vesicular acetylcholine transporter in cholinergic nerve terminals and its targeting to a specific population of small synaptic vesicles. Proceedings of the National Academy of Sciences of the United States of America, 93(8), 3547–3552.

    Article  PubMed  CAS  Google Scholar 

  31. Zhang, H., Wu, C. Y., Wang, W., & Harrington, M. A. (2011). Interneuronal synapses formed by motor neurons appear to be glutamatergic. Neuroreport, 22(16), 809–813. doi:10.1097/WNR.0b013e32834b6d5c.

    PubMed  Google Scholar 

  32. Sanchez-Ponce, D., Tapia, M., Munoz, A., & Garrido, J. J. (2008). New role of IKK alpha/beta phosphorylated I kappa B alpha in axon outgrowth and axon initial segment development. Molecular and Cellular Neuroscience, 37(4), 832–844. doi:10.1016/j.mcn.2008.01.010.

    Article  PubMed  CAS  Google Scholar 

  33. Garner, C. C., Waites, C. L., & Ziv, N. E. (2006). Synapse development: Still looking for the forest, still lost in the trees. Cell and Tissue Research, 326(2), 249–262. doi:10.1007/s00441-006-0278-1.

    Article  PubMed  Google Scholar 

  34. Hayashi, M. K., Tang, C., Verpelli, C., Narayanan, R., Stearns, M. H., Xu, R. M., et al. (2009). The postsynaptic density proteins Homer and Shank form a polymeric network structure. Cell, 137(1), 159–171. doi:10.1016/j.cell.2009.01.050.

    Article  PubMed  CAS  Google Scholar 

  35. Boeckers, T. M. (2006). The postsynaptic density. Cell and Tissue Research, 326(2), 409–422. doi:10.1007/s00441-006-0274-5.

    Article  PubMed  CAS  Google Scholar 

  36. Han, K., & Kim, E. (2008). Synaptic adhesion molecules and PSD-95. Progress in Neurobiology, 84(3), 263–283. doi:10.1016/j.pneurobio.2007.10.011.

    Article  PubMed  CAS  Google Scholar 

  37. Grabrucker, A. M., Knight, M. J., Proepper, C., Bockmann, J., Joubert, M., Rowan, M., et al. (2011). Concerted action of zinc and ProSAP/Shank in synaptogenesis and synapse maturation. The EMBO Journal, 30(3), 569–581. doi:10.1038/emboj.2010.336.

    Article  PubMed  CAS  Google Scholar 

  38. Song, J. Y., Ichtchenko, K., Sudhof, T. C., & Brose, N. (1999). Neuroligin 1 is a postsynaptic cell-adhesion molecule of excitatory synapses. Proceedings of the National Academy of Sciences of the United States of America, 96(3), 1100–1105.

    Article  PubMed  CAS  Google Scholar 

  39. Blasi, J., Chapman, E. R., Link, E., Binz, T., Yamasaki, S., De Camilli, P., et al. (1993). Botulinum neurotoxin A selectively cleaves the synaptic protein SNAP-25. Nature, 365(6442), 160–163. doi:10.1038/365160a0.

    Article  PubMed  CAS  Google Scholar 

  40. Hu, B. Y., Weick, J. P., Yu, J., Ma, L. X., Zhang, X. Q., Thomson, J. A., et al. (2010). Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency. Proceedings of the National Academy of Sciences of the United States of America, 107(9), 4335–4340. doi:10.1073/pnas.0910012107.

    Article  PubMed  CAS  Google Scholar 

  41. Ko, J. Y., Park, C. H., Koh, H. C., Cho, Y. H., Kyhm, J. H., Kim, Y. S., et al. (2007). Human embryonic stem cell-derived neural precursors as a continuous, stable, and on-demand source for human dopamine neurons. Journal of Neurochemistry, 103(4), 1417–1429. doi:10.1111/j.1471-4159.2007.04898.x.

    Article  PubMed  CAS  Google Scholar 

  42. Liu, G. H., Barkho, B. Z., Ruiz, S., Diep, D., Qu, J., Yang, S. L., et al. (2011). Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome. Nature, 472(7342), 221–225. doi:10.1038/nature09879.

    Article  PubMed  CAS  Google Scholar 

  43. Itzhaki, I., Maizels, L., Huber, I., Zwi-Dantsis, L., Caspi, O., Winterstern, A., et al. (2011). Modelling the long QT syndrome with induced pluripotent stem cells. Nature, 471(7337), 225–229. doi:10.1038/nature09747.

    Article  PubMed  CAS  Google Scholar 

  44. Dimos, J. T., Rodolfa, K. T., Niakan, K. K., Weisenthal, L. M., Mitsumoto, H., Chung, W., et al. (2008). Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science, 321(5893), 1218–1221. doi:10.1126/science.1158799.

    Article  PubMed  CAS  Google Scholar 

  45. Inoue, H. (2010). Neurodegenerative disease-specific induced pluripotent stem cell research. Experimental Cell Research, 316(16), 2560–2564. doi:10.1016/j.yexcr.2010.04.022.

    Article  PubMed  CAS  Google Scholar 

  46. Boulting, G. L., Kiskinis, E., Croft, G. F., Amoroso, M. W., Oakley, D. H., Wainger, B. J., et al. (2011). A functionally characterized test set of human induced pluripotent stem cells. Nature Biotechnology. doi:10.1038/nbt.1783.

  47. Kim, J. E., O’Sullivan, M. L., Sanchez, C. A., Hwang, M., Israel, M. A., Brennand, K., et al. (2011). Investigating synapse formation and function using human pluripotent stem cell-derived neurons. Proceedings of the National Academy of Sciences of the United States of America, 108(7), 3005–3010. doi:10.1073/pnas.1007753108.

    Article  PubMed  CAS  Google Scholar 

  48. Wichterle, H., Lieberam, I., Porter, J. A., & Jessell, T. M. (2002). Directed differentiation of embryonic stem cells into motor neurons. Cell, 110(3), 385–397.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Sabine Seltenheim for excellent technical support, the central electron microscopy unit of Ulm University for help with embedding and electron microscopy setups, Frank Edenhofer (Bonn, Germany) for providing recombinant Cre protein and Gustavo Mostoslavsky for providing the reprogramming vector construct. This study was supported by the Deutsche Forschungsgemeinschaft (SFB497/B8 to TMB and DFG BO1718/4-1 to StL and TMB).

Conflict of Interest

None.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Stefan Liebau or Tobias M. Boeckers.

Additional information

Marianne Stockmann and Leonhard Linta contributed equally

Electronic supplementary materials

Below is the link to the electronic supplementary material.

ESM 1

(DOCX 23 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stockmann, M., Linta, L., Föhr, K.J. et al. Developmental and Functional Nature of Human iPSC Derived Motoneurons. Stem Cell Rev and Rep 9, 475–492 (2013). https://doi.org/10.1007/s12015-011-9329-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12015-011-9329-4

Keywords

Navigation