title: Differentiation from human pluripotent stem cells of cortical neurons of the superficial layers amenable to psychiatric disease modeling and high-throughput drug screening.
abstract: Cortical neurons of the superficial layers (II-IV) represent a pivotal neuronal population involved in the higher cognitive functions of the human and are particularly affected by psychiatric diseases with developmental manifestations such as schizophrenia and autism. Differentiation protocols of human pluripotent stem cells (PSC) into cortical neurons have been achieved, opening the way to in vitro modeling of neuropsychiatric diseases. However, these protocols commonly result in the asynchronous production of neurons typical for the different layers of the cortex within an extended period of culture, thus precluding the analysis of specific subtypes of neurons in a standardized manner. Addressing this issue, we have successfully captured a stable population of self-renewing late cortical progenitors (LCPs) that synchronously and massively differentiate into glutamatergic cortical neurons of the upper layers. The short time course of differentiation into neurons of these progenitors has made them amenable to high-throughput assays. This has allowed us to analyze the capability of LCPs at differentiating into post mitotic neurons as well as extending and branching neurites in response to a collection of selected bioactive molecules. LCPs and cortical neurons of the upper layers were successfully produced from patient-derived-induced PSC, indicating that this system enables functional studies of individual-specific cortical neurons ex vivo for disease modeling and therapeutic purposes.
authors: Neuroplasticity and Therapeutics, CECS, I-STEM, AFM, Evry Cedex, France.
authors: C
authors: C
authors: Boissart
authors: A
authors: A
authors: Poulet
authors: P
authors: P
authors: Georges
authors: H
authors: H
authors: Darville
authors: E
authors: E
authors: Julita
authors: R
authors: R
authors: Delorme
authors: T
authors: T
authors: Bourgeron
authors: M
authors: M
authors: Peschanski
authors: A
authors: A
authors: Benchoua
mesh_terms: D001321:Autistic Disorder; D002454:Cell Differentiation; D002540:Cerebral Cortex / Q000166:cytology*; D057166:High-Throughput Screening Assays; D006801:Humans; D008954:Models, Biological; D009474:Neurons / Q000166:cytology*; D039904:Pluripotent Stem Cells / Q000166:cytology*
references: Nat Neurosci. 2012 Dec;15(12):1667-74
references: 23143522
references: Cell Stem Cell. 2010 May 7;6(5):407-11
references: 20452313
references: Mol Psychiatry. 2011 Aug;16(8):867-80
references: 20479760
references: Oncogene. 2002 Dec 5;21(55):8470-6
references: 12466966
references: J Cell Biol. 2000 Apr 17;149(2):263-70
references: 10769020
references: Nat Biotechnol. 2008 Jan;26(1):101-6
references: 18059259
references: J Mol Cell Biol. 2012 Jun;4(3):180-3
references: 22430918
references: Arch Gen Psychiatry. 1998 Mar;55(3):215-24
references: 9510215
references: Eur J Neurosci. 2009 Aug;30(3):449-63
references: 19656176
references: Cell. 2010 Nov 12;143(4):527-39
references: 21074045
references: Mol Psychiatry. 2006 Jun;11(6):557-66
references: 16402129
references: Nat Biotechnol. 2009 Mar;27(3):275-80
references: 19252484
references: J Biomol Screen. 1999;4(2):67-73
references: 10838414
references: Stem Cell Res Ther. 2012 Apr 18;3(2):14
references: 22512921
references: Nature. 2010 Mar 25;464(7288):554-561
references: 20154730
references: Neuropsychopharmacology. 2010 Jan;35(1):350-1
references: 20010716
references: Development. 2005 Mar;132(6):1295-304
references: 15750183
references: J Comp Neurol. 1992 Jul 8;321(2):223-40
references: 1500541
references: J Cell Biol. 2011 Jun 13;193(6):985-94
references: 21670212
references: J Child Adolesc Psychopharmacol. 2006 Oct;16(5):525-40
references: 17069542
references: Development. 2012 Oct;139(20):3870-9
references: 22951639
references: Cereb Cortex. 2000 Oct;10(10):927-38
references: 11007543
references: Brain Res. 2005 Aug 2;1052(1):71-81
references: 16018988
references: Front Mol Neurosci. 2011 Aug 09;4:16
references: 21886606
references: Cell Stem Cell. 2008 Nov 6;3(5):519-32
references: 18983967
references: Nature. 2005 Sep 1;437(7055):64-7
references: 16136130
references: Nat Neurosci. 2012 Feb 05;15(3):477-86, S1
references: 22306606
references: J Neurosci. 2011 Feb 2;31(5):1676-87
references: 21289176
references: Neurology. 2009 Sep 8;73(10):742-3
references: 19625704
references: Mol Psychiatry. 2012 Dec;17(12):1239-53
references: 22472874
references: Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12770-5
references: 22761314
references: Recent Pat CNS Drug Discov. 2008 Nov;3(3):200-8
references: 18991809
references: Hum Mol Genet. 2010 Apr 15;19(R1):R71-6
references: 20418487
references: Brain Res. 2010 Jan 14;1309:83-94
references: 19896929
references: Nat Protoc. 2013 Jan;8(1):111-30
references: 23257981
references: BioDrugs. 2010 Apr 1;24(2):99-108
references: 20199125
references: Nature. 2011 May 12;473(7346):221-5
references: 21490598
references: Nat Genet. 2007 Jan;39(1):25-7
references: 17173049
references: Front Mol Neurosci. 2011 Nov 01;4:35
references: 22053151
references: Cereb Cortex. 2011 Mar;21(3):588-96
references: 20624841
references: Trends Neurosci. 2002 Apr;25(4):191-9
references: 11998687
references: Proc Natl Acad Sci U S A. 2011 Aug 23;108(34):14169-74
references: 21807996
references: Development. 2012 Apr;139(7):1247-57
references: 22357933
references: Nat Protoc. 2012 Oct;7(10):1836-46
references: 22976355