title: Capture of neuroepithelial-like stem cells from pluripotent stem cells provides a versatile system for in vitro production of human neurons.
abstract: Human embryonic stem cells (hESC) and induced pluripotent stem cells (iPSC) provide new prospects for studying human neurodevelopment and modeling neurological disease. In particular, iPSC-derived neural cells permit a direct comparison of disease-relevant molecular pathways in neurons and glia derived from patients and healthy individuals. A prerequisite for such comparative studies are robust protocols that efficiently yield standardized populations of neural cell types. Here we show that long-term self-renewing neuroepithelial-like stem cells (lt-NES cells) derived from 3 hESC and 6 iPSC lines in two independent laboratories exhibit consistent characteristics including i) continuous expandability in the presence of FGF2 and EGF; ii) stable neuronal and glial differentiation competence; iii) characteristic transcription factor profile; iv) hindbrain specification amenable to regional patterning; v) capacity to generate functionally mature human neurons. We further show that lt-NES cells are developmentally distinct from fetal tissue-derived radial glia-like stem cells. We propose that lt-NES cells provide an interesting tool for studying human neurodevelopment and may serve as a standard system to facilitate comparative analyses of hESC and hiPSC-derived neural cells from control and diseased genetic backgrounds.
authors.affiliation: Department of Biochemistry, Wellcome Trust Centre for Stem Cell Research, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Anna
authors.initials: A
authors.lastname: Falk
authors.forename: Philipp
authors.initials: P
authors.lastname: Koch
authors.forename: Jaideep
authors.initials: J
authors.lastname: Kesavan
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takashima
authors.forename: Julia
authors.initials: J
authors.lastname: Ladewig
authors.forename: Michael
authors.initials: M
authors.lastname: Alexander
authors.forename: Ole
authors.initials: O
authors.lastname: Wiskow
authors.forename: Jignesh
authors.initials: J
authors.lastname: Tailor
authors.forename: Matthew
authors.initials: M
authors.lastname: Trotter
authors.forename: Steven
authors.initials: S
authors.lastname: Pollard
authors.forename: Austin
authors.initials: A
authors.lastname: Smith
authors.forename: Oliver
authors.initials: O
authors.lastname: Brüstle
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D016000:Cluster Analysis; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D046569:Neuroepithelial Cells / Q000166:cytology* / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D014157:Transcription Factors; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor