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

Ralda Nehme | Zendy; Emanuela Zuccaro | Zendy; Sulagna Ghosh | Zendy; Chenchen Li | Zendy; J. L. Sherwood | Zendy; Olli Pietiläinen | Zendy; Lindy E. Barrett | Zendy; Francesco Limone | Zendy; Kathleen A. Worringer | Zendy; Sravya Kommineni | Zendy; Ying Zang | Zendy; Davide Cacchiarelli | Zendy; Alex Meissner | Zendy; Rolf Adolfsson | Zendy; Stephen J. Haggarty | Zendy; Jon M. Madison | Zendy; Mathias Müller | Zendy; Paola Arlotta | Zendy; Zhanyan Fu | Zendy; Guoping Feng | Zendy; Kevin Eggan | Zendy

Open Access

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

Author(s) -

Ralda Nehme,

Emanuela Zuccaro,

Sulagna Ghosh,

Chenchen Li,

J. L. Sherwood,

Olli Pietiläinen,

Lindy E. Barrett,

Francesco Limone,

Kathleen A. Worringer,

Sravya Kommineni,

Ying Zang,

Davide Cacchiarelli,

Alex Meissner,

Rolf Adolfsson,

Stephen J. Haggarty,

Jon M. Madison,

Mathias Müller,

Paola Arlotta,

Zhanyan Fu,

Guoping Feng,

Kevin Eggan

Publication year - 2018

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2018.04.066

Subject(s) - neuroscience , biology , glutamatergic , excitatory postsynaptic potential , ganglionic eminence , neurotransmission , induced pluripotent stem cell , cellular differentiation , glutamate receptor , progenitor cell , embryonic stem cell , microbiology and biotechnology , stem cell , inhibitory postsynaptic potential , gene , genetics , receptor

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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