Generation of anterior foregut endoderm from human embryonic and induced pluripotent stem cells

被引:280
作者
Green, Michael D. [1 ,2 ]
Chen, Antonia [1 ,2 ]
Nostro, Maria-Cristina [3 ,4 ]
d'Souza, Sunita L. [1 ,2 ]
Schaniel, Christoph [1 ,2 ]
Lemischka, Ihor R. [1 ,2 ]
Gouon-Evans, Valerie [1 ,2 ]
Keller, Gordon [3 ,4 ]
Snoeck, Hans-Willem [1 ,2 ]
机构
[1] Mt Sinai Sch Med, Dept Gene & Cell Med, New York, NY USA
[2] Mt Sinai Sch Med, Black Family Stem Cell Inst, New York, NY USA
[3] Ontario Canc Inst, Div Stem Cell & Dev Biol, Toronto, ON M4X 1K9, Canada
[4] Ontario Canc Inst, McEwen Ctr Regenerat Med, Toronto, ON M4X 1K9, Canada
关键词
DIFFERENTIATION; SPECIFICATION; EXPRESSION; INDUCTION; ES;
D O I
10.1038/nbt.1788
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Directed differentiation of human embryonic stem (hES) cells and human induced pluripotent stem (hiPS) cells captures in vivo developmental pathways for specifying lineages in vitro, thus avoiding perturbation of the genome with exogenous genetic material. Thus far, derivation of endodermal lineages has focused predominantly on hepatocytes, pancreatic endocrine cells and intestinal cells(1-5). The ability to differentiate pluripotent cells into anterior foregut endoderm (AFE) derivatives would expand their utility for cell therapy and basic research to tissues important for immune function, such as the thymus; for metabolism, such as thyroid and parathyroid; and for respiratory function, such as trachea and lung. We find that dual inhibition of transforming growth factor (TGF)-beta and bone morphogenic protein (BMP) signaling after specification of definitive endoderm from pluripotent cells results in a highly enriched AFE population that is competent to be patterned along dorsoventral and anteroposterior axes. These findings provide an approach for the generation of AFE derivatives.
引用
收藏
页码:267 / U153
页数:7
相关论文
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