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Combining NGN2 Programming with Developmental Patterning Generates Human Excitatory Neurons with NMDAR-Mediated Synaptic Transmission
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2018 (English)In: Cell reports, ISSN 2211-1247, E-ISSN 2211-1247, Vol. 23, no 8, p. 2509-2523Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Cell Press , 2018. Vol. 23, no 8, p. 2509-2523
National Category
Neurosciences Cell and Molecular Biology
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URN: urn:nbn:se:umu:diva-148731DOI: 10.1016/j.celrep.2018.04.066ISI: 000433052200026PubMedID: 29791859Scopus ID: 2-s2.0-85047221405OAI: oai:DiVA.org:umu-148731DiVA, id: diva2:1221160
Available from: 2018-06-19 Created: 2018-06-19 Last updated: 2018-06-19Bibliographically approved

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