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Generation of pure GABAergic neurons by transcription factor programming

Yang, Nan ; Chanda, Soham ; Marro, Samuele ; Ng, Yi Han ; Janas, Justyna A. ; Haag, Daniel ; Ang, Cheen Euong ; Tang, Yunshuo ; Flores, Quetzal and Mall, Moritz , et al. (2017) In Nature Methods 14(6). p.621-628
Abstract

Approaches to differentiating pluripotent stem cells (PSCs) into neurons currently face two major challenges-(i) generated cells are immature, with limited functional properties; and (ii) cultures exhibit heterogeneous neuronal subtypes and maturation stages. Using lineage-determining transcription factors, we previously developed a single-step method to generate glutamatergic neurons from human PSCs. Here, we show that transient expression of the transcription factors Ascl1 and Dlx2 (AD) induces the generation of exclusively GABAergic neurons from human PSCs with a high degree of synaptic maturation. These AD-induced neuronal (iN) cells represent largely nonoverlapping populations of GABAergic neurons that express various... (More)

Approaches to differentiating pluripotent stem cells (PSCs) into neurons currently face two major challenges-(i) generated cells are immature, with limited functional properties; and (ii) cultures exhibit heterogeneous neuronal subtypes and maturation stages. Using lineage-determining transcription factors, we previously developed a single-step method to generate glutamatergic neurons from human PSCs. Here, we show that transient expression of the transcription factors Ascl1 and Dlx2 (AD) induces the generation of exclusively GABAergic neurons from human PSCs with a high degree of synaptic maturation. These AD-induced neuronal (iN) cells represent largely nonoverlapping populations of GABAergic neurons that express various subtype-specific markers. We further used AD-iN cells to establish that human collybistin, the loss of gene function of which causes severe encephalopathy, is required for inhibitory synaptic function. The generation of defined populations of functionally mature human GABAergic neurons represents an important step toward enabling the study of diseases affecting inhibitory synaptic transmission.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Methods
volume
14
issue
6
pages
621 - 628
publisher
Nature Publishing Group
external identifiers
  • scopus:85021779995
  • pmid:28504679
ISSN
1548-7091
DOI
10.1038/nmeth.4291
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2017 Nature America, Inc. All rights reserved.
id
feecba21-a5d0-47a6-a8a8-c820e4bcb5b8
date added to LUP
2025-08-26 11:18:22
date last changed
2025-08-26 12:11:08
@article{feecba21-a5d0-47a6-a8a8-c820e4bcb5b8,
  abstract     = {{<p>Approaches to differentiating pluripotent stem cells (PSCs) into neurons currently face two major challenges-(i) generated cells are immature, with limited functional properties; and (ii) cultures exhibit heterogeneous neuronal subtypes and maturation stages. Using lineage-determining transcription factors, we previously developed a single-step method to generate glutamatergic neurons from human PSCs. Here, we show that transient expression of the transcription factors Ascl1 and Dlx2 (AD) induces the generation of exclusively GABAergic neurons from human PSCs with a high degree of synaptic maturation. These AD-induced neuronal (iN) cells represent largely nonoverlapping populations of GABAergic neurons that express various subtype-specific markers. We further used AD-iN cells to establish that human collybistin, the loss of gene function of which causes severe encephalopathy, is required for inhibitory synaptic function. The generation of defined populations of functionally mature human GABAergic neurons represents an important step toward enabling the study of diseases affecting inhibitory synaptic transmission.</p>}},
  author       = {{Yang, Nan and Chanda, Soham and Marro, Samuele and Ng, Yi Han and Janas, Justyna A. and Haag, Daniel and Ang, Cheen Euong and Tang, Yunshuo and Flores, Quetzal and Mall, Moritz and Wapinski, Orly and Li, Mavis and Ahlenius, Henrik and Rubenstein, John L. and Chang, Howard Y. and Buylla, Arturo Alvarez and Südhof, Thomas C. and Wernig, Marius}},
  issn         = {{1548-7091}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{6}},
  pages        = {{621--628}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Methods}},
  title        = {{Generation of pure GABAergic neurons by transcription factor programming}},
  url          = {{http://dx.doi.org/10.1038/nmeth.4291}},
  doi          = {{10.1038/nmeth.4291}},
  volume       = {{14}},
  year         = {{2017}},
}