title: Pharmacological characterisation of ligand- and voltage-gated ion channels expressed in human iPSC-derived forebrain neurons.
abstract: BACKGROUND
  Genetic causes, or predisposition, are increasingly accepted to be part of the ethiopathogenesis of many neuropsychiatric diseases. While genes can be studied in any type of cells, their physiological function in human brain cells is difficult to evaluate, particularly in living subjects.
  
  
  METHODS
  As a first step towards the characterisation of human inducible pluripotent stem cell (iPSC)-derived neurons from autism spectrum disorder (ASD) patients, we used gene expression and functional studies to define the regional identity of the typical forebrain differentiation, demonstrate expression patterns of genes of interest in ASD and understand the properties of 'control' iPSC-derived neurons (iCell-Neurons™), with a focus on receptors and ion channels that play a central role in synaptic physio-pathology.
  
  
  CONCLUSIONS
  The gene expression profile of the iCell-Neurons™ closely resembled that observed in neonatal prefrontal cortex tissues. Functional studies, performed mainly using calcium flux assays, demonstrated the presence of ionotropic glutamate (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartate) and gamma-aminobutyric acid type A receptors. Voltage-gated sodium and calcium channels were also identified using similar techniques.
  
  
  CONCLUSIONS
  Overall, the results reported here suggest that iCell-Neurons™ are a good cellular model of a relatively immature forebrain human neuron population that can be used both as a control in comparison to patients cells, and as host cells in which mutations, insertions and deletions can be used in order to study the molecular mechanisms of ASD and other neurological disorders in an isogenic cellular background.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, 46285, USA.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Dage
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Colvin
authors.forename: Antoine
authors.initials: A
authors.lastname: Fouillet
authors.forename: Emily
authors.initials: E
authors.lastname: Langron
authors.forename: William C
authors.initials: WC
authors.lastname: Roell
authors.forename: Jingling
authors.initials: J
authors.lastname: Li
authors.forename: Sachin X
authors.initials: SX
authors.lastname: Mathur
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Mogg
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Schmitt
authors.forename: Christian C
authors.initials: CC
authors.lastname: Felder
authors.forename: Kalpana M
authors.initials: KM
authors.lastname: Merchant
authors.forename: John
authors.initials: J
authors.lastname: Isaac
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Broad
authors.forename: Emanuele
authors.initials: E
authors.lastname: Sher
authors.forename: Daniel
authors.initials: D
authors.lastname: Ursu
mesh_terms: D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects / Q000502:physiology*; D007473:Ion Channels / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D016548:Prosencephalon / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D018079:Receptors, GABA / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D058468:Receptors, Ionotropic Glutamate / Q000819:agonists / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D007473:Ion Channels; D012333:RNA, Messenger; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D058468:Receptors, Ionotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D061566:Voltage-Gated Sodium Channels; D002118:Calcium