Specification of functional cranial placode derivatives from human pluripotent stem cells. Academic Article uri icon

Overview

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.

publication date

  • November 27, 2013

Research

keywords

  • Cell Differentiation
  • Cell Lineage
  • Embryonic Stem Cells
  • Endocrine Cells
  • Neurons
  • Pluripotent Stem Cells

Identity

PubMed Central ID

  • PMC3887225

Scopus Document Identifier

  • 84890143546

Digital Object Identifier (DOI)

  • 10.1038/nature12298

PubMed ID

  • 24290755

Additional Document Info

volume

  • 5

issue

  • 5