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Esophageal Organoids from Human Pluripotent Stem Cells Delineate Sox2 Functions during Esophageal Specification.

Cell stem cell | 2018

Tracheal and esophageal disorders are prevalent in humans and difficult to accurately model in mice. We therefore established a three-dimensional organoid model of esophageal development through directed differentiation of human pluripotent stem cells. Sequential manipulation of bone morphogenic protein (BMP), Wnt, and RA signaling pathways was required to pattern definitive endoderm into foregut, anterior foregut (AFG), and dorsal AFG spheroids. Dorsal AFG spheroids grown in a 3D matrix formed human esophageal organoids (HEOs), and HEO cells could be transitioned into two-dimensional cultures and grown as esophageal organotypic rafts. In both configurations, esophageal tissues had proliferative basal progenitors and a differentiated stratified squamous epithelium. Using HEO cultures to model human esophageal birth defects, we identified that Sox2 promotes esophageal specification in part through repressing Wnt signaling in dorsal AFG and promoting survival. Consistently, Sox2 ablation in mice causes esophageal agenesis. Thus, HEOs present a powerful platform for modeling human pathologies and tissue engineering.

Pubmed ID: 30244869 RIS Download

Additional research tools detected in this publication

Antibodies used in this publication

Associated grants

  • Agency: NICHD NIH HHS, United States
    Id: P01 HD093363
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK078392
  • Agency: NIAID NIH HHS, United States
    Id: R37 AI045898
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM063483
  • Agency: NIAID NIH HHS, United States
    Id: U19 AI116491
  • Agency: NIBIB NIH HHS, United States
    Id: U18 EB021780

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