title: Genetically engineering self-organization of human pluripotent stem cells into a liver bud-like tissue using Gata6.
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.
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02139, USA.|MIT Emergent Behaviors of Integrated Cellular Systems (EBICS) Center, Cambridge, Massachusetts 02139, USA.|Synthetic Biology Center, MIT, Cambridge, Massachusetts 02139, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Guye
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02139, USA.|MIT Emergent Behaviors of Integrated Cellular Systems (EBICS) Center, Cambridge, Massachusetts 02139, USA.
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Ebrahimkhani
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02139, USA.|MIT Emergent Behaviors of Integrated Cellular Systems (EBICS) Center, Cambridge, Massachusetts 02139, USA.|Synthetic Biology Center, MIT, Cambridge, Massachusetts 02139, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Kipniss
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02139, USA.
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Velazquez
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02139, USA.|MIT Emergent Behaviors of Integrated Cellular Systems (EBICS) Center, Cambridge, Massachusetts 02139, USA.|Synthetic Biology Center, MIT, Cambridge, Massachusetts 02139, USA.
authors.forename: Eldi
authors.initials: E
authors.lastname: Schoenfeld
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02139, USA.|Synthetic Biology Center, MIT, Cambridge, Massachusetts 02139, USA.
authors.forename: Samira
authors.initials: S
authors.lastname: Kiani
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02139, USA.|MIT Emergent Behaviors of Integrated Cellular Systems (EBICS) Center, Cambridge, Massachusetts 02139, USA.
authors.forename: Linda G
authors.initials: LG
authors.lastname: Griffith
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02139, USA.|MIT Emergent Behaviors of Integrated Cellular Systems (EBICS) Center, Cambridge, Massachusetts 02139, USA.|Synthetic Biology Center, MIT, Cambridge, Massachusetts 02139, USA.
authors.forename: Ron
authors.initials: R
authors.lastname: Weiss
mesh_terms: D002454:Cell Differentiation; D002460:Cell Line; D050993:GATA6 Transcription Factor / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000502:physiology*; D005818:Genetic Engineering / Q000379:methods*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects*; D008099:Liver / Q000254:growth & development*
chemical_list: D050993:GATA6 Transcription Factor; C494759:GATA6 protein, human