Pluripotent stem cell differentiation reveals distinct developmental pathways regulating lung- versus thyroid-lineage specification. Academic Article uri icon

Overview

abstract

  • The in vitro-directed differentiation of pluripotent stem cells (PSCs) through stimulation of developmental signaling pathways can generate mature somatic cell types for basic laboratory studies or regenerative therapies. However, there has been significant uncertainty regarding a method to separately derive lung versus thyroid epithelial lineages, as these two cell types each originate from Nkx2-1+ foregut progenitors and the minimal pathways claimed to regulate their distinct lineage specification in vivo or in vitro have varied in previous reports. Here, we employ PSCs to identify the key minimal signaling pathways (Wnt+BMP versus BMP+FGF) that regulate distinct lung- versus thyroid-lineage specification, respectively, from foregut endoderm. In contrast to most previous reports, these minimal pathways appear to be evolutionarily conserved between mice and humans, and FGF signaling, although required for thyroid specification, unexpectedly appears to be dispensable for lung specification. Once specified, distinct Nkx2-1+ lung or thyroid progenitor pools can now be independently derived for functional 3D culture maturation, basic developmental studies or future regenerative therapies.

publication date

  • September 25, 2017

Research

keywords

  • Body Patterning
  • Cell Differentiation
  • Lung
  • Pluripotent Stem Cells
  • Signal Transduction
  • Thyroid Gland

Identity

PubMed Central ID

  • PMC5702071

Scopus Document Identifier

  • 85032839888

Digital Object Identifier (DOI)

  • 10.1038/nm0298-201

PubMed ID

  • 28947536

Additional Document Info

volume

  • 144

issue

  • 21