Citation

Close JL, Yao Z, Levi BP, Miller JA, Bakken TE, Menon V, Ting JT, Wall A, Krostag AR, Thomsen ER, Nelson AM, Mich JK, Hodge RD, Shehata SI, Glass IA, Bort S, Shapovalova NV, Ngo NK, Grimley JS, Phillips JW, Thompson CL, Ramanathan S, Lein E. 2017. Single-Cell Profiling of an In Vitro Model of Human Interneuron Development Reveals Temporal Dynamics of Cell Type Production and Maturation. Neuron. 93(5):1035-1048.e5. Pubmed: 28279351 DOI:S0896-6273(17)30098-3

Abstract

GABAergic interneurons are essential for neural circuit function, and their loss or dysfunction is implicated in human neuropsychiatric disease. In vitro methods for interneuron generation hold promise for studying human cellular and functional properties and, ultimately, for therapeutic cell replacement. Here we describe a protocol for generating cortical interneurons from hESCs and analyze the properties and maturation time course of cell types using single-cell RNA-seq. We find that the cell types produced mimic in vivo temporal patterns of neuron and glial production, with immature progenitors and neurons observed early and mature cortical neurons and glial cell types produced late. By comparing the transcriptomes of immature interneurons to those of more mature neurons, we identified genes important for human interneuron differentiation. Many of these genes were previously implicated in neurodevelopmental and neuropsychiatric disorders.
Copyright © 2017 Elsevier Inc. All rights reserved.

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Sharad Ramanathan investigates how multi-potent stem cells make fate decisions to give rise to complex human tissues, and how the dynamics of key neurons in the nervous system drive behavioral decisions.

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