title: Multipotent caudal neural progenitors derived from human pluripotent stem cells that give rise to lineages of the central and peripheral nervous system.
abstract: The caudal neural plate is a distinct region of the embryo that gives rise to major progenitor lineages of the developing central and peripheral nervous system, including neural crest and floor plate cells. We show that dual inhibition of the glycogen synthase kinase 3β and activin/nodal pathways by small molecules differentiate human pluripotent stem cells (hPSCs) directly into a preneuroepithelial progenitor population we named "caudal neural progenitors" (CNPs). CNPs coexpress caudal neural plate and mesoderm markers, and, share high similarities to embryonic caudal neural plate cells in their lineage differentiation potential. Exposure of CNPs to BMP2/4, sonic hedgehog, or FGF2 signaling efficiently directs their fate to neural crest/roof plate cells, floor plate cells, and caudally specified neuroepithelial cells, respectively. Neural crest derived from CNPs differentiated to neural crest derivatives and demonstrated extensive migratory properties in vivo. Importantly, we also determined the key extrinsic factors specifying CNPs from human embryonic stem cell include FGF8, canonical WNT, and IGF1. Our studies are the first to identify a multipotent neural progenitor derived from hPSCs, that is the precursor for major neural lineages of the embryonic caudal neural tube.
authors.affiliation: Department of Anatomy and Neurosciences, University of Melbourne, Melbourne, Australia.|Danish Research Institute of Translational Neuroscience, Aarhus University, Aarhus, Denmark.
authors.forename: Mark
authors.initials: M
authors.lastname: Denham
authors.affiliation: Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto, Japan.|InStem, NCBS, Bangalore, Karnataka, India.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: Murdoch Children's Research Institute, Melbourne, Australia.
authors.forename: Trevelyan
authors.initials: T
authors.lastname: Menheniott
authors.affiliation: Murdoch Children's Research Institute, Melbourne, Australia.
authors.forename: Ben
authors.initials: B
authors.lastname: Rollo
authors.affiliation: Murdoch Children's Research Institute, Melbourne, Australia.
authors.forename: Dongcheng
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Anatomy and Neurosciences, University of Melbourne, Melbourne, Australia.
authors.forename: Shelley
authors.initials: S
authors.lastname: Hough
authors.affiliation: Centre for Neural Engineering, Department of Electrical and Electronic Engineering, University of Melbourne, Melbourne, Australia.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Alshawaf
authors.affiliation: Danish Research Institute of Translational Neuroscience, Aarhus University, Aarhus, Denmark.
authors.forename: Fabia
authors.initials: F
authors.lastname: Febbraro
authors.affiliation: Murdoch Children's Research Institute, Melbourne, Australia.
authors.forename: Samiramis
authors.initials: S
authors.lastname: Ighaniyan
authors.affiliation: Department of Anatomy and Neurosciences, University of Melbourne, Melbourne, Australia.
authors.forename: Jessie
authors.initials: J
authors.lastname: Leung
authors.affiliation: Murdoch Children's Research Institute, Melbourne, Australia.
authors.forename: David A
authors.initials: DA
authors.lastname: Elliott
authors.affiliation: Murdoch Children's Research Institute, Melbourne, Australia.
authors.forename: Donald F
authors.initials: DF
authors.lastname: Newgreen
authors.affiliation: Department of Anatomy and Neurosciences, University of Melbourne, Melbourne, Australia.|Walter and Eliza Hall Institute, Melbourne, Australia.|Florey Institute of Neuroscience and Mental Health, Melbourne, Australia.
authors.forename: Martin F
authors.initials: MF
authors.lastname: Pera
authors.affiliation: Department of Anatomy and Neurosciences, University of Melbourne, Melbourne, Australia.|Centre for Neural Engineering, Department of Electrical and Electronic Engineering, University of Melbourne, Melbourne, Australia.
authors.forename: Mirella
authors.initials: M
authors.lastname: Dottori
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D002490:Central Nervous System / Q000166:cytology*; D008648:Mesoderm / Q000166:cytology; D008810:Mice, Inbred C57BL; D009432:Neural Crest / Q000166:cytology*; D054258:Neural Plate / Q000166:cytology; D058953:Neural Stem Cells / Q000166:cytology*; D054259:Neural Tube / Q000166:cytology*; D046569:Neuroepithelial Cells / Q000166:cytology; D017933:Peripheral Nervous System / Q000166:cytology*; D039904:Pluripotent Stem Cells / Q000166:cytology*; D017207:Rats, Sprague-Dawley
keywords: Floor plate; Human embryonic stem cells; Neural crest; Peripheral nervous system; Roof plate