Letter | Published:

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

Nature Biotechnology volume 29, pages 267272 (2011) | Download Citation

Abstract

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 cells1,2,3,4,5. 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)-β 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.

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Acknowledgements

This work was supported by NYSTEM grant NO8G-422 to H.-W.S.

Author information

Affiliations

  1. Department of Gene and Cell Medicine and Black Family Stem Cell Institute, Mount Sinai School of Medicine, New York, New York, USA.

    • Michael D Green
    • , Antonia Chen
    • , Sunita L d'Souza
    • , Christoph Schaniel
    • , Ihor R Lemischka
    • , Valerie Gouon-Evans
    •  & Hans-Willem Snoeck
  2. Division of Stem Cell and Developmental Biology and McEwen Centre for Regenerative Medicine, Ontario Cancer Institute, Toronto, Ontario, Canada.

    • Maria-Cristina Nostro
    •  & Gordon Keller

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Contributions

M.D.G. performed all experiments with assistance of A.C. M.-C.N., V.G.-E., S.L.S. and G.K. advised and assisted with induction of definitive endoderm. S.L.S., I.R.L. and C.S. generated and characterized the hiPS lines, respectively. M.D.G. and H.-W.S. designed the experiments and wrote the manuscript.

Competing interests

A patent application filed with the US Patent and Trade Office by M.G. and H.W.S. on the work reported in this article is pending.

Corresponding author

Correspondence to Hans-Willem Snoeck.

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DOI

https://doi.org/10.1038/nbt.1788

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