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Cell Rep DOI:10.1016/j.celrep.2018.04.066

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

Publication TypeJournal Article
Year of Publication2018
AuthorsNehme, R, Zuccaro, E, Ghosh, SDia, Li, C, Sherwood, JL, Pietilainen, O, Barrett, LE, Limone, F, Worringer, KA, Kommineni, S, Zang, Y, Cacchiarelli, D, Meissner, A, Adolfsson, R, Haggarty, S, Madison, J, Muller, M, Arlotta, P, Fu, Z, Feng, G, Eggan, K
JournalCell Rep
Volume23
Issue8
Pages2509-2523
Date Published2018 May 22
ISSN2211-1247
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.

DOI10.1016/j.celrep.2018.04.066
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/29791859?dopt=Abstract

Alternate JournalCell Rep
PubMed ID29791859
PubMed Central IDPMC6003669
Grant ListU01 MH105669 / MH / NIMH NIH HHS / United States
U01 MH115727 / MH / NIMH NIH HHS / United States