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

Patrick Guye (), Mohammad R. Ebrahimkhani, Nathan Kipniss, Jeremy J. Velazquez, Eldi Schoenfeld, Samira Kiani, Linda G. Griffith and Ron Weiss ()
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Patrick Guye: Massachusetts Institute of Technology (MIT)
Mohammad R. Ebrahimkhani: Massachusetts Institute of Technology (MIT)
Nathan Kipniss: Massachusetts Institute of Technology (MIT)
Jeremy J. Velazquez: Massachusetts Institute of Technology (MIT)
Eldi Schoenfeld: Massachusetts Institute of Technology (MIT)
Samira Kiani: Massachusetts Institute of Technology (MIT)
Linda G. Griffith: Massachusetts Institute of Technology (MIT)
Ron Weiss: Massachusetts Institute of Technology (MIT)

Nature Communications, 2016, vol. 7, issue 1, 1-12

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms10243

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