title: Single-Cell Profiling of an In Vitro Model of Human Interneuron Development Reveals Temporal Dynamics of Cell Type Production and Maturation.
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.
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98109, USA. Electronic address: jenniec@alleninstitute.org.
authors.forename: Jennie L
authors.initials: JL
authors.lastname: Close
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98109, USA.
authors.forename: Zizhen
authors.initials: Z
authors.lastname: Yao
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98109, USA.
authors.forename: Boaz P
authors.initials: BP
authors.lastname: Levi
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98109, USA.
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Miller
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98109, USA.
authors.forename: Trygve E
authors.initials: TE
authors.lastname: Bakken
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98109, USA.
authors.forename: Vilas
authors.initials: V
authors.lastname: Menon
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98109, USA.
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Ting
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98109, USA.
authors.forename: Abigail
authors.initials: A
authors.lastname: Wall
authors.affiliation: Bluebird Bio, Seattle, WA 98102, USA.
authors.forename: Anne-Rachel
authors.initials: AR
authors.lastname: Krostag
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98109, USA.
authors.forename: Elliot R
authors.initials: ER
authors.lastname: Thomsen
authors.affiliation: Allen Institute for Cell Science, Seattle, WA 98109, USA.
authors.forename: Angel M
authors.initials: AM
authors.lastname: Nelson
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98109, USA.
authors.forename: John K
authors.initials: JK
authors.lastname: Mich
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98109, USA.
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Hodge
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98109, USA.
authors.forename: Soraya I
authors.initials: SI
authors.lastname: Shehata
authors.affiliation: Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195, USA.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Glass
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98109, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Bort
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98109, USA.
authors.forename: Nadiya V
authors.initials: NV
authors.lastname: Shapovalova
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98109, USA.
authors.forename: N Kiet
authors.initials: NK
authors.lastname: Ngo
authors.affiliation: Universal Cells, Seattle, WA 98109, USA.
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Grimley
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98109, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Phillips
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98109, USA.
authors.forename: Carol L
authors.initials: CL
authors.lastname: Thompson
authors.affiliation: Molecular and Cellular Biology Department, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Sharad
authors.initials: S
authors.lastname: Ramanathan
authors.affiliation: Allen Institute for Brain Science, Seattle, WA 98109, USA.
authors.forename: Ed
authors.initials: E
authors.lastname: Lein
mesh_terms: D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D059330:GABAergic Neurons / Q000166:cytology*; D006801:Humans; D007395:Interneurons / Q000166:cytology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology; D009457:Neuroglia / Q000166:cytology*; D059010:Single-Cell Analysis; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D014157:Transcription Factors
keywords: MGE; human cortex; interneurons; single-cell RNA-seq