title: Specification of functional cranial placode derivatives from human pluripotent stem cells.
abstract: Cranial placodes are embryonic structures essential for sensory and endocrine organ development. Human placode development has remained largely inaccessible despite the serious medical conditions caused by the dysfunction of placode-derived tissues. Here, we demonstrate the efficient derivation of cranial placodes from human pluripotent stem cells. Timed removal of the BMP inhibitor Noggin, a component of the dual-SMAD inhibition strategy of neural induction, triggers placode induction at the expense of CNS fates. Concomitant inhibition of fibroblast growth factor signaling disrupts placode derivation and induces surface ectoderm. Further fate specification at the preplacode stage enables the selective generation of placode-derived trigeminal ganglia capable of in vivo engraftment, mature lens fibers, and anterior pituitary hormone-producing cells that upon transplantation produce human growth hormone and adrenocorticotropic hormone in vivo. Our results establish a powerful experimental platform to study human cranial placode development and set the stage for the development of human cell-based therapies in sensory and endocrine disease.
authors.affiliation: Center for Stem Cell Biology, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, USA; Developmental Biology Program, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, USA; Weill Graduate School of Medical Sciences of Cornell University, New York, NY 10021, USA.
authors.forename: Zehra
authors.initials: Z
authors.lastname: Dincer
authors.affiliation: Center for Stem Cell Biology, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, USA; Department of Neurosurgery, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, USA.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Piao
authors.affiliation: Center for Stem Cell Biology, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, USA; Developmental Biology Program, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Niu
authors.affiliation: Center for Stem Cell Biology, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, USA; Developmental Biology Program, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, USA.
authors.forename: Yosif
authors.initials: Y
authors.lastname: Ganat
authors.affiliation: Center for Stem Cell Biology, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, USA; Developmental Biology Program, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, USA.
authors.forename: Sonja
authors.initials: S
authors.lastname: Kriks
authors.affiliation: Center for Stem Cell Biology, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, USA; Developmental Biology Program, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, USA.
authors.forename: Bastian
authors.initials: B
authors.lastname: Zimmer
authors.affiliation: Center for Stem Cell Biology, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, USA; Developmental Biology Program, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, USA.
authors.forename: Song-Hai
authors.initials: SH
authors.lastname: Shi
authors.affiliation: Center for Stem Cell Biology, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, USA; Department of Neurosurgery, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, USA.
authors.forename: Viviane
authors.initials: V
authors.lastname: Tabar
authors.affiliation: Center for Stem Cell Biology, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, USA; Developmental Biology Program, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, USA; Department of Neurosurgery, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, USA. Electronic address: studerl@mskcc.org.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Studer
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D055098:Endocrine Cells / Q000166:cytology* / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005855:Germ Layers / Q000166:cytology; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D007908:Lens, Crystalline / Q000166:cytology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D064531:Peripherins / Q000235:genetics / Q000378:metabolism; D010902:Pituitary Gland / Q000166:cytology; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D012668:Trigeminal Ganglion / Q000166:cytology; D000099176:Noggin Protein
chemical_list: D000324:Adrenocorticotropic Hormone; D002352:Carrier Proteins; D005346:Fibroblast Growth Factors; D013006:Growth Hormone; D064531:Peripherins; D000099176:Noggin Protein; C578994:PRPH protein, human