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Genetically engineering self-organization of human pluripotent stem cells into a liver bud-like tissue using Gata6

Author

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  • Patrick Guye

    (Massachusetts Institute of Technology (MIT)
    MIT Emergent Behaviors of Integrated Cellular Systems (EBICS) Center
    Synthetic Biology Center, MIT)

  • Mohammad R. Ebrahimkhani

    (Massachusetts Institute of Technology (MIT)
    MIT Emergent Behaviors of Integrated Cellular Systems (EBICS) Center)

  • Nathan Kipniss

    (Massachusetts Institute of Technology (MIT)
    MIT Emergent Behaviors of Integrated Cellular Systems (EBICS) Center
    Synthetic Biology Center, MIT)

  • Jeremy J. Velazquez

    (Massachusetts Institute of Technology (MIT))

  • Eldi Schoenfeld

    (Massachusetts Institute of Technology (MIT)
    MIT Emergent Behaviors of Integrated Cellular Systems (EBICS) Center
    Synthetic Biology Center, MIT)

  • Samira Kiani

    (Massachusetts Institute of Technology (MIT)
    Synthetic Biology Center, MIT)

  • Linda G. Griffith

    (Massachusetts Institute of Technology (MIT)
    MIT Emergent Behaviors of Integrated Cellular Systems (EBICS) Center)

  • Ron Weiss

    (Massachusetts Institute of Technology (MIT)
    MIT Emergent Behaviors of Integrated Cellular Systems (EBICS) Center
    Synthetic Biology Center, MIT)

Abstract

Human induced pluripotent stem cells (hiPSCs) have potential for personalized and regenerative medicine. While most of the methods using these cells have focused on deriving homogenous populations of specialized cells, there has been modest success in producing hiPSC-derived organotypic tissues or organoids. Here we present a novel approach for generating and then co-differentiating hiPSC-derived progenitors. With a genetically engineered pulse of GATA-binding protein 6 (GATA6) expression, we initiate rapid emergence of all three germ layers as a complex function of GATA6 expression levels and tissue context. Within 2 weeks we obtain a complex tissue that recapitulates early developmental processes and exhibits a liver bud-like phenotype, including haematopoietic and stromal cells as well as a neuronal niche. Collectively, our approach demonstrates derivation of complex tissues from hiPSCs using a single autologous hiPSCs as source and generates a range of stromal cells that co-develop with parenchymal cells to form tissues.

Suggested Citation

  • Patrick Guye & Mohammad R. Ebrahimkhani & Nathan Kipniss & Jeremy J. Velazquez & Eldi Schoenfeld & Samira Kiani & Linda G. Griffith & Ron Weiss, 2016. "Genetically engineering self-organization of human pluripotent stem cells into a liver bud-like tissue using Gata6," Nature Communications, Nature, vol. 7(1), pages 1-12, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10243
    DOI: 10.1038/ncomms10243
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    Cited by:

    1. William C. W. Chen & Leonid Gaidukov & Yong Lai & Ming-Ru Wu & Jicong Cao & Michael J. Gutbrod & Gigi C. G. Choi & Rachel P. Utomo & Ying-Chou Chen & Liliana Wroblewska & Manolis Kellis & Lin Zhang & , 2022. "A synthetic transcription platform for programmable gene expression in mammalian cells," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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