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Generation of pure GABAergic neurons by transcription factor programming
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Journal Article
Generation of pure GABAergic neurons by transcription factor programming
2017
Overview
Transient transcription factor expression rapidly induces a homogenous population of mature GABAergic neurons from human pluripotent stem cells, aiding the study of inhibitory neuron function and disease.
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.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ 13/106
/ 631/378
/ Animals
/ Basic Helix-Loop-Helix Transcription Factors - genetics
/ Biomedical Engineering/Biotechnology
/ Cell Differentiation - genetics
/ GABAergic Neurons - cytology
/ GABAergic Neurons - physiology
/ Glia
/ Homeodomain Proteins - genetics
/ Humans
/ Mice
/ Neurons
/ Pluripotent Stem Cells - cytology
/ Pluripotent Stem Cells - physiology
