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

Nat Commun. 2016 Jan 6;7:10243. doi: 10.1038/ncomms10243.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Differentiation
  • Cell Line
  • GATA6 Transcription Factor / pharmacology*
  • Gene Expression Regulation / physiology*
  • Genetic Engineering / methods*
  • Humans
  • Induced Pluripotent Stem Cells / drug effects*
  • Liver / growth & development*

Substances

  • GATA6 Transcription Factor
  • GATA6 protein, human