HNF4A is essential for specification of hepatic progenitors from human pluripotent stem cells

Ann DeLaForest, Masato Nagaoka, Karim Si-Tayeb, Fallon K. Noto, Genevieve Konopka, Michele A. Battle, Stephen A. Duncan

Research output: Contribution to journalArticle

125 Scopus citations

Abstract

The availability of pluripotent stem cells offers the possibility of using such cells to model hepatic disease and development. With this in mind, we previously established a protocol that facilitates the differentiation of both human embryonic stem cells and induced pluripotent stem cells into cells that share many characteristics with hepatocytes. The use of highly defined culture conditions and the avoidance of feeder cells or embryoid bodies allowed synchronous and reproducible differentiation to occur. The differentiation towards a hepatocyte-like fate appeared to recapitulate many of the developmental stages normally associated with the formation of hepatocytes in vivo. In the current study, we addressed the feasibility of using human pluripotent stem cells to probe the molecular mechanisms underlying human hepatocyte differentiation. We demonstrate (1) that human embryonic stem cells express a number of mRNAs that characterize each stage in the differentiation process, (2) that gene expression can be efficiently depleted throughout the differentiation time course using shRNAs expressed from lentiviruses and (3) that the nuclear hormone receptor HNF4A is essential for specification of human hepatic progenitor cells by establishing the expression of the network of transcription factors that controls the onset of hepatocyte cell fate.

Original languageEnglish (US)
Pages (from-to)4143-4153
Number of pages11
JournalDevelopment
Volume138
Issue number19
DOIs
StatePublished - Oct 1 2011

Keywords

  • HNF4A
  • Hepatocyte differentiation
  • Human pluripotent stem cells

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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    DeLaForest, A., Nagaoka, M., Si-Tayeb, K., Noto, F. K., Konopka, G., Battle, M. A., & Duncan, S. A. (2011). HNF4A is essential for specification of hepatic progenitors from human pluripotent stem cells. Development, 138(19), 4143-4153. https://doi.org/10.1242/dev.062547