title: Transcriptome and in Vitro Differentiation Profile of Human Embryonic Stem Cell Derived NKX2.1-Positive Neural Progenitors.
abstract: The generation of inhibitory interneuron progenitors from human embryonic stem cells (ESCs) is of great interest due to their potential use in transplantation therapies designed to treat central nervous system disorders. The medial ganglionic eminence (MGE) is a transient embryonic structure in the ventral telencephalon that is a major source of cortical GABAergic inhibitory interneuron progenitors. These progenitors migrate tangentially to sites in the cortex and differentiate into a variety of interneuron subtypes, forming local synaptic connections with excitatory projection neurons to modulate activity of the cortical circuitry. The homeobox domain-containing transcription factor NKX2.1 is highly expressed in the MGE and pre-optic area of the ventral subpallium and is essential for specifying cortical interneuron fate. Using a combination of growth factor agonists and antagonists to specify ventral telencephalic fates, we previously optimized a protocol for the efficient generation of NKX2.1-positive MGE-like neural progenitors from human ESCs. To establish their identity, we now characterize the transcriptome of these MGE-like neural progenitors using RNA sequencing and demonstrate the capacity of these cells to differentiate into inhibitory interneurons in vitro using a neuron-astrocyte co-culture system. These data provide information on the potential origin of interneurons in the human brain.
authors.affiliation: Department of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT, 06459, USA. cychen@wesleyan.edu.
authors.forename: Christopher Y
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Department of Genetics and Genome Sciences, Institute for Systems Genomics, 400 Farmington Avenue, UCONN Health, Farmington, CT, 06030, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Plocik
authors.affiliation: Department of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT, 06459, USA.
authors.forename: Nickesha C
authors.initials: NC
authors.lastname: Anderson
authors.affiliation: Department of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT, 06459, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Moakley
authors.affiliation: Department of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT, 06459, USA.
authors.forename: Trinithas
authors.initials: T
authors.lastname: Boyi
authors.affiliation: Department of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT, 06459, USA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Dundes
authors.affiliation: Department of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT, 06459, USA.
authors.forename: Chelsea
authors.initials: C
authors.lastname: Lassiter
authors.affiliation: Department of Genetics and Genome Sciences, Institute for Systems Genomics, 400 Farmington Avenue, UCONN Health, Farmington, CT, 06030, USA.
authors.forename: Brenton R
authors.initials: BR
authors.lastname: Graveley
authors.affiliation: Department of Biology, Wesleyan University, 52 Lawn Avenue, Middletown, CT, 06459, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Grabel
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D000066449:Human Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007395:Interneurons / Q000166:cytology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics*; D059467:Transcriptome
chemical_list: C000614414:Nkx2-1 protein, mouse; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors
keywords: Differential gene expression; Medial ganglionic eminence; NKX2.1; RNA-sequencing; Transcriptome