Open AccessUse of hPSC-derived 3D organoids and mouse genetics to define the roles of YAP in the development of the esophagus
Author(s) -
Dominique D. Bailey,
Yongchun Zhang,
Benjamin J. van Soldt,
Ming Jiang,
Supriya Suresh,
Hiroshi Nakagawa,
Anil K. Rustgi,
Seema S. Aceves,
Wellington V. Cardoso
Publication year - 2019
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.178855
Subject(s) - biology , esophagus , progenitor cell , organoid , progenitor , induced pluripotent stem cell , stem cell , microbiology and biotechnology , cell growth , developmental biology , embryonic stem cell , anatomy , genetics , gene
Balanced progenitor activities are critical for the development and maintenance of high turn-over organs such as the esophagus. However, the molecular mechanisms regulating these progenitor activities in the esophagus remain to be elucidated. Here, we demonstrated that Yap is required for the proliferation of esophageal progenitor cells (EPCs) in the developing murine esophagus. We found that Yap deficiency reduces EPC proliferation and stratification while persistent Yap activation increases cell proliferation and causes aberrant stratification of the developing esophagus. We further demonstrated that the role of YAP signaling is conserved in the developing human esophagus by utilizing 3D human pluripotent stem cell (hPSC)-derived esophageal organoid culture. Taken together, our studies combing loss/gain-of-function murine models and hPSC differentiation support a key role for YAP in the self-renewal of EPCs and stratification of the esophageal epithelium.