3D Modeling of Esophageal Development Using Human PSC-Derived Basal Progenitors Reveals a Critical Role for Notch Signaling

Overview

Journal Cell Stem Cell

Publisher Cell Press

Specialty Cell Biology

Date 2018 Sep 25

PMID 30244870

Citations 49

Authors

Yongchun Zhang

Ying Yang

Ming Jiang

Sarah Xuelian Huang

Wanwei Zhang

Denise Al Alam

Soula Danopoulos

Munemasa Mori

Ya-Wen Chen

Revathi Balasubramanian

Susana M Chuva de Sousa Lopes

Carlos Serra

Monika Bialecka

Eugene Kim

Sijie Lin

Ana Luisa Rodrigues Toste de Carvalho

Paul N Riccio

Wellington V Cardoso

Xin Zhang

Hans-Willem Snoeck

Jianwen Que

Affiliations

Soon will be listed here.

Abstract

Pluripotent stem cells (PSCs) could provide a powerful system to model development of the human esophagus, whose distinct tissue organization compared to rodent esophagus suggests that developmental mechanisms may not be conserved between species. We therefore established an efficient protocol for generating esophageal progenitor cells (EPCs) from human PSCs. We found that inhibition of TGF-ß and BMP signaling is required for sequential specification of EPCs, which can be further purified using cell-surface markers. These EPCs resemble their human fetal counterparts and can recapitulate normal development of esophageal stratified squamous epithelium during in vitro 3D cultures and in vivo. Importantly, combining hPSC differentiation strategies with mouse genetics elucidated a critical role for Notch signaling in the formation of this epithelium. These studies therefore not only provide an efficient approach to generate EPCs, but also offer a model system to study the regulatory mechanisms underlying development of the human esophagus.

Citing Articles

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