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  Combining NGN2 Programming with Developmental Patterning Generates Human Excitatory Neurons with NMDAR-Mediated Synaptic Transmission

Nehme, R., Zuccaro, E., Ghosh, S. D., Li, C., Sherwood, J. L., Pietilainen, O., et al. (2018). Combining NGN2 Programming with Developmental Patterning Generates Human Excitatory Neurons with NMDAR-Mediated Synaptic Transmission. Cell Reports, 23(8), 2509-2523. doi:10.1016/j.celrep.2018.04.066.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0003-4C39-9 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-4C3A-8
Genre: Journal Article

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 Creators:
Nehme, Ralda , Author
Zuccaro, Emanuela , Author
Ghosh, Sulagna Dia , Author
Li, Chenchen , Author
Sherwood, John L. , Author
Pietilainen, Olli , Author
Barrett, Lindy E., Author
Limone, Francesco , Author
Worringer, Kathleen A. , Author
Kommineni, Sravya , Author
Zang, Ying , Author
Cacchiarelli, Davide , Author
Meissner, Alex1, 2, Author              
Adolfsson, Rolf , Author
Haggarty, Stephen , Author
Madison, Jon , Author
Muller, Matthias , Author
Arlotta, Paola , Author
Fu, Zhanyan , Author
Feng, Guoping , Author
Eggan, Kevin, Author more..
Affiliations:
1Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2379694              
2Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA, ou_persistent22              

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Free keywords: AMPAR; CAMK2A; NGN2; NMDAR; Wnt inhibition; dual SMAD inhibition; excitatory neurons; human stem cell; neuronal differentiation; single cell profiling
 Abstract: Transcription factor programming of pluripotent stem cells (PSCs) has emerged as an approach to generate human neurons for disease modeling. However, programming schemes produce a variety of cell types, and those neurons that are made often retain an immature phenotype, which limits their utility in modeling neuronal processes, including synaptic transmission. We report that combining NGN2 programming with SMAD and WNT inhibition generates human patterned induced neurons (hpiNs). Single-cell analyses showed that hpiN cultures contained cells along a developmental continuum, ranging from poorly differentiated neuronal progenitors to well-differentiated, excitatory glutamatergic neurons. The most differentiated neurons could be identified using a CAMK2A::GFP reporter gene and exhibited greater functionality, including NMDAR-mediated synaptic transmission. We conclude that utilizing single-cell and reporter gene approaches for selecting successfully programmed cells for study will greatly enhance the utility of hpiNs and other programmed neuronal populations in the modeling of nervous system disorders.

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Language(s): eng - English
 Dates: 2018-04-142018-05-22
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1016/j.celrep.2018.04.066
 Degree: -

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Title: Cell Reports
Source Genre: Journal
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Publ. Info: Maryland Heights, MO : Cell Press
Pages: 15 Volume / Issue: 23 (8) Sequence Number: - Start / End Page: 2509 - 2523 Identifier: ISSN: 2211-1247
CoNE: https://pure.mpg.de/cone/journals/resource/2211-1247