Esophageal Organoids from Human Pluripotent Stem Cells Delineate Sox2 Functions during Esophageal Specification.
Esophageal Organoids from Human Pluripotent Stem Cells Delineate Sox2 Functions during Esophageal Specification.
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DOI：
10.1016/j.stem.2018.08.008
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发表时间：
2018-10-04
期刊：
影响因子：
23.9
通讯作者：
Wells JM
中科院分区：
文献类型：
--
作者：
Trisno SL;Philo KED;McCracken KW;Catá EM;Ruiz-Torres S;Rankin SA;Han L;Nasr T;Chaturvedi P;Rothenberg ME;Mandegar MA;Wells SI;Zorn AM;Wells JM
气管和食管疾病在人类中普遍存在，并且难以在小鼠中准确建模。因此，我们通过人多能干细胞的定向分化建立了食管发育的三维类器官模型。BMP，WNT和RA信号通路的顺序操作是必需的图案定形内胚层成前肠，前前肠（AFG），和背AFG球体。在三维基质中生长的背AFG球体形成人食管类器官（HEO），HEO细胞可以过渡到二维培养物中并作为食管器官型筏生长。在这两种结构中，食管组织具有增殖的基底祖细胞和分化的复层鳞状上皮。使用HEO培养物模拟人食管出生缺陷，我们确定Sox 2部分通过抑制背侧AFG中的Wnt信号传导和促进存活来促进食管特异性。一致地，Sox 2消融小鼠导致食管发育不全。因此，HEO为人类病理学和组织工程建模提供了一个强大的平台。Trisno等人已经通过多能干细胞的定向分化产生了人食管类器官（HEO）。HEO含有食管祖细胞和分化的复层鳞状上皮。使用HEO来模拟前肠发育揭示了SOX 2通过调节Wnt信号传导来调节NKX 2 -1。
Tracheal and esophageal disorders are prevalent in humans and are 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 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. Trisno et al have generated human esophageal organoids (HEOs) through the directed differentiation of pluripotent stem cells. HEOs contain esophageal progenitors and a differentiated stratified squamous epithelium. Using HEOs to model foregut development revealed that SOX2 regulates NKX2–1 through modulation of Wnt signaling.
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影响因子：
2.5
作者：
Kormish, Jay D.;Sinner, Debora;Zorn, Aaron M.
通讯作者：
Zorn, Aaron M.
人类肺发育和疾病的三维模型来自多能干细胞。
影响因子：
21.3
作者：
Chen YW;Huang SX;de Carvalho ALRT;Ho SH;Islam MN;Volpi S;Notarangelo LD;Ciancanelli M;Casanova JL;Bhattacharya J;Liang AF;Palermo LM;Porotto M;Moscona A;Snoeck HW
通讯作者：
Snoeck HW
影响因子：
4.6
作者：
Domyan, Eric T.;Ferretti, Elisabetta;Sun, Xin
通讯作者：
Sun, Xin
DOI：
10.1073/pnas.0902274106
发表时间：
2009-09-22
影响因子：
11.1
作者：
Harris-Johnson, Kelley S.;Domyan, Eric T.;Sun, Xin
通讯作者：
Sun, Xin
影响因子：
30.8
作者：
Fantes, J;Ragge, NK;FitzPatrick, DR
通讯作者：
FitzPatrick, DR