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

Cell Stem Cell
Stephen L TrisnoJames M Wells

Abstract

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.

Citations

May 11, 2019·PloS One·Michael E BregenzerGeeta Mehta
Oct 3, 2019·Genes & Development·Melissa H Little, Alexander N Combes
Jul 6, 2019·Médecine sciences : M/S·Charlotte FlatresMaxime M Mahé
Oct 17, 2019·Annual Review of Physiology·Yongchun Zhang, Jianwen Que
Feb 27, 2020·Nature Reviews. Gastroenterology & Hepatology·Harry Cheuk Hay LauJun Yu
Apr 7, 2020·Journal of Molecular Cell Biology·Juan HeDong Gao
Jul 14, 2020·American Journal of Physiology. Gastrointestinal and Liver Physiology·Akaljot SinghMichael A Helmrath
Apr 18, 2019·Development·Emily M HollowayJason R Spence
Jul 18, 2020·Journal of Hematology & Oncology·Michele ZanoniAnna Tesei
Sep 19, 2019·Journal of the Royal Society of Medicine·Greg Maguire
Dec 12, 2019·Frontiers in Pediatrics·Rémi Doucet-LadevèzeCarine Blanchard
Feb 26, 2020·Nature Biotechnology·Nathaniel J HogrebeJeffrey R Millman
Jul 9, 2020·Nature Reviews. Molecular Cell Biology·Jihoon KimJuergen A Knoblich
Oct 24, 2020·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Su-Jin Lee, Hyang-Ae Lee
Jan 9, 2021·Cell Death & Disease·Xuan WangYunfang Wang
Feb 16, 2021·Frontiers in Bioengineering and Biotechnology·Chrysanthi-Maria MoysidouRóisín Meabh Owens
Nov 19, 2020·Cell Death and Differentiation·Masaaki FunataTakanori Takebe
Dec 16, 2020·Cells·Peter W Nagle, Robert P Coppes
Feb 11, 2021·Genes·Maxwell C Hakun, Bin Gu
Nov 23, 2020·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Allison LewisAnne Grapin-Botton
Jan 29, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Kuancan LiuXiaopeng Lan
Mar 7, 2020·Cell Stem Cell·Arun SharmaClive N Svendsen
Mar 31, 2021·Development·Yongchun ZhangJianwen Que
Apr 12, 2021·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Hirofumi Kiyokawa, Mitsuru Morimoto
May 24, 2021·Developmental Biology·Nicole A EdwardsAaron M Zorn
Jun 19, 2021·Nature Cancer·Yuan-Hung LoCalvin J Kuo
Jun 16, 2021·Cell Stem Cell·Yoku HayakawaTimothy C Wang
Jul 15, 2021·Pathology Oncology Research : POR·Dingqing FengBin Ling
Jul 31, 2021·Frontiers in Cell and Developmental Biology·Virginie Barbet, Laura Broutier
Aug 1, 2021·Experimental Cell Research·Reihaneh Alsadat MahmoudianMohammad Reza Abbaszadegan
Aug 14, 2021·Acta Pharmaceutica Sinica. B·Yuanjin ZhangXin Wang

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