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

Yongchun Zhang, Ying Yang, Ming Jiang, 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 & 1 others Jianwen Que

Research output: Contribution to journalArticle

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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. Que, Zhang, and colleagues established an efficient approach to differentiate human pluripotent stem cells (hPSCs) into esophageal progenitor cells (EPCs). Combined use of hPSC-derived EPCs and mouse genetic models demonstrates the important role of BMP and NOTCH signaling in promoting squamous differentiation of EPCs.

LanguageEnglish
Pages516-529.e5
JournalCell Stem Cell
Volume23
Issue number4
DOIs
StatePublished - Oct 4 2018

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Pluripotent Stem Cells
Human Development
Stem Cells
Esophagus
Epithelium
Genetic Models
Cell Differentiation
Rodentia

Keywords

  • basal cells
  • BMP
  • esophagus
  • human embryonic stem cells
  • human-induced pluripotent stem cell
  • NOTCH
  • organoids
  • TGF-ß
  • WNT

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

Cite this

3D Modeling of Esophageal Development using Human PSC-Derived Basal Progenitors Reveals a Critical Role for Notch Signaling. / Zhang, Yongchun; Yang, Ying; Jiang, Ming; Huang, Xuelian; Zhang, Wanwei; Al Alam, Denise; Danopoulos, Soula; Mori, Munemasa; Chen, Ya Wen; Balasubramanian, Revathi; Chuva de Sousa Lopes, Susana M.; Serra, Carlos; Bialecka, Monika; Kim, Eugene; Lin, Sijie; Toste de Carvalho, Ana Luisa Rodrigues; Riccio, Paul N.; Cardoso, Wellington V.; Zhang, Xin; Snoeck, Hans Willem; Que, Jianwen.

In: Cell Stem Cell, Vol. 23, No. 4, 04.10.2018, p. 516-529.e5.

Research output: Contribution to journalArticle

Zhang, Y, Yang, Y, Jiang, M, Huang, X, Zhang, W, Al Alam, D, Danopoulos, S, Mori, M, Chen, YW, Balasubramanian, R, Chuva de Sousa Lopes, SM, Serra, C, Bialecka, M, Kim, E, Lin, S, Toste de Carvalho, ALR, Riccio, PN, Cardoso, WV, Zhang, X, Snoeck, HW & Que, J 2018, '3D Modeling of Esophageal Development using Human PSC-Derived Basal Progenitors Reveals a Critical Role for Notch Signaling' Cell Stem Cell, vol. 23, no. 4, pp. 516-529.e5. https://doi.org/10.1016/j.stem.2018.08.009
Zhang, Yongchun ; Yang, Ying ; Jiang, Ming ; Huang, Xuelian ; Zhang, Wanwei ; Al Alam, Denise ; Danopoulos, Soula ; Mori, Munemasa ; Chen, Ya Wen ; Balasubramanian, Revathi ; Chuva de Sousa Lopes, Susana M. ; Serra, Carlos ; Bialecka, Monika ; Kim, Eugene ; Lin, Sijie ; Toste de Carvalho, Ana Luisa Rodrigues ; Riccio, Paul N. ; Cardoso, Wellington V. ; Zhang, Xin ; Snoeck, Hans Willem ; Que, Jianwen. / 3D Modeling of Esophageal Development using Human PSC-Derived Basal Progenitors Reveals a Critical Role for Notch Signaling. In: Cell Stem Cell. 2018 ; Vol. 23, No. 4. pp. 516-529.e5.
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AU - Zhang, Wanwei

AU - Al Alam, Denise

AU - Danopoulos, Soula

AU - Mori, Munemasa

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AU - Balasubramanian, Revathi

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AU - Snoeck, Hans Willem

AU - Que, Jianwen

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