Specification of Functional Cranial Placode Derivatives from Human Pluripotent Stem Cells

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 c...

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Main Authors: Zehra Dincer, Jinghua Piao, Lei Niu, Yosif Ganat, Sonja Kriks, Bastian Zimmer, Song-Hai Shi, Viviane Tabar, Lorenz Studer
Format: Article
Language:English
Published: Elsevier 2013-12-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124713006475
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author Zehra Dincer
Jinghua Piao
Lei Niu
Yosif Ganat
Sonja Kriks
Bastian Zimmer
Song-Hai Shi
Viviane Tabar
Lorenz Studer
author_facet Zehra Dincer
Jinghua Piao
Lei Niu
Yosif Ganat
Sonja Kriks
Bastian Zimmer
Song-Hai Shi
Viviane Tabar
Lorenz Studer
author_sort Zehra Dincer
collection DOAJ
description 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.
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spelling doaj.art-eaf00f37677d4733a437c68bc0ab578f2022-12-21T23:31:53ZengElsevierCell Reports2211-12472013-12-01551387140210.1016/j.celrep.2013.10.048Specification of Functional Cranial Placode Derivatives from Human Pluripotent Stem CellsZehra Dincer0Jinghua Piao1Lei Niu2Yosif Ganat3Sonja Kriks4Bastian Zimmer5Song-Hai Shi6Viviane Tabar7Lorenz Studer8Center for Stem Cell Biology, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, USACenter for Stem Cell Biology, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, USACenter for Stem Cell Biology, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, USACenter for Stem Cell Biology, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, USACenter for Stem Cell Biology, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, USACenter for Stem Cell Biology, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, USACenter for Stem Cell Biology, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, USACenter for Stem Cell Biology, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, USACenter for Stem Cell Biology, Sloan-Kettering Institute, 1275 York Ave, New York, NY 10065, USACranial 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.http://www.sciencedirect.com/science/article/pii/S2211124713006475
spellingShingle Zehra Dincer
Jinghua Piao
Lei Niu
Yosif Ganat
Sonja Kriks
Bastian Zimmer
Song-Hai Shi
Viviane Tabar
Lorenz Studer
Specification of Functional Cranial Placode Derivatives from Human Pluripotent Stem Cells
Cell Reports
title Specification of Functional Cranial Placode Derivatives from Human Pluripotent Stem Cells
title_full Specification of Functional Cranial Placode Derivatives from Human Pluripotent Stem Cells
title_fullStr Specification of Functional Cranial Placode Derivatives from Human Pluripotent Stem Cells
title_full_unstemmed Specification of Functional Cranial Placode Derivatives from Human Pluripotent Stem Cells
title_short Specification of Functional Cranial Placode Derivatives from Human Pluripotent Stem Cells
title_sort specification of functional cranial placode derivatives from human pluripotent stem cells
url http://www.sciencedirect.com/science/article/pii/S2211124713006475
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