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  Functional Maturation of Human Stem Cell-Derived Neurons in Long-Term Cultures

Lam, R. S., Töpfer, F., Wood, P. G., Busskamp, V., & Bamberg, E. (2017). Functional Maturation of Human Stem Cell-Derived Neurons in Long-Term Cultures. PLoS One, 12(1): e0169506. doi:10.1371/journal.pone.0169506.

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 Creators:
Lam, Rebecca S.1, Author           
Töpfer, Felix1, Author           
Wood, Philip G.1, Author           
Busskamp, Volker2, Author
Bamberg, Ernst1, Author           
Affiliations:
1Department of Biophysical Chemistry, Max Planck Institute of Biophysics, Max Planck Society, ou_2068289              
2Center for Regenerative Therapies Dresden, TU-Dresden, Germany, ou_persistent22              

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 Abstract: Differentiated neurons can be rapidly acquired, within days, by inducing stem cells to express neurogenic transcription factors. We developed a protocol to maintain long-term cultures of human neurons, called iNGNs, which are obtained by inducing Neurogenin-1 and Neurogenin-2 expression in induced pluripotent stem cells. We followed the functional development of iNGNs over months and they showed many hallmark properties for neuronal maturation, including robust electrical and synaptic activity. Using iNGNs expressing a variant of channelrhodopsin-2, called CatCh, we could control iNGN activity with blue light stimulation. In combination with optogenetic tools, iNGNs offer opportunities for studies that require precise spatial and temporal resolution. iNGNs developed spontaneous network activity, and these networks had excitatory glutamatergic synapses, which we characterized with single-cell synaptic recordings. AMPA glutamatergic receptor activity was especially dominant in postsynaptic recordings, whereas NMDA glutamatergic receptor activity was absent from postsynaptic recordings but present in extrasynaptic recordings. Our results on long-term cultures of iNGNs could help in future studies elucidating mechanisms of human synaptogenesis and neurotransmission, along with the ability to scale-up the size of the cultures.

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Language(s): eng - English
 Dates: 2016-09-212016-12-192017-01-04
 Publication Status: Published online
 Pages: 26
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1371/journal.pone.0169506
 Degree: -

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Title: PLoS One
Source Genre: Journal
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Publ. Info: San Francisco, CA : Public Library of Science
Pages: - Volume / Issue: 12 (1) Sequence Number: e0169506 Start / End Page: - Identifier: ISSN: 1932-6203
CoNE: https://pure.mpg.de/cone/journals/resource/1000000000277850