Format

Send to

Choose Destination
Cell Rep. 2013 Dec 12;5(5):1387-402. doi: 10.1016/j.celrep.2013.10.048. Epub 2013 Nov 27.

Specification of functional cranial placode derivatives from human pluripotent stem cells.

Author information

1
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.
2
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.
3
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.
4
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.

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.

PMID:
24290755
PMCID:
PMC3887225
DOI:
10.1016/j.celrep.2013.10.048
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center