Phenotype reversion in fetal human liver epithelial cells identifies the role of an intermediate meso-endodermal stage before hepatic maturation

Mari Inada, Antonia Follenzi, Kang Cheng, Manju Surana, Brigid Joseph, Daniel Benten, Sriram Bandi, Hong Qian, Sanjeev Gupta

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Understanding the biological potential of fetal stem/progenitor cells will help define mechanisms in liver development and homeostasis. We isolated epithelial fetal human liver cells and established phenotype-specific changes in gene expression during continuous culture conditions. Fetal human liver epithelial cells displayed stem cell properties with multilineage gene expression, extensive proliferation and generation of mesenchymal lineage cells, although the initial epithelial phenotype was rapidly supplanted by meso-endodermal phenotype in culture. This meso-endodermal phenotype was genetically regulated through cytokine signaling, including transforming growth factor β, bone morphogenetic protein, fibroblast growth factor and other signaling pathways. Reactivation of HNF3α (FOXA1) transcription factor, a driver of hepatic specification in the primitive endoderm, indicated that the meso-endodermal phenotype represented an earlier developmental stage of cells. We found that fetal liver epithelial cells formed mature hepatocytes in vivo, including after genetic manipulation using lentiviral vectors, offering convenient assays for analysis of further cell differentiation and fate. Taken together, these studies demonstrate plasticity in fetal liver epithelial stem cells, offer paradigms for defining mechanisms regulating lineage switching in stem cells, and provide potential avenues for regulating cell phenotypes for applications of stem cells, such as for cell therapy.

Original languageEnglish (US)
Pages (from-to)1002-1013
Number of pages12
JournalJournal of Cell Science
Volume121
Issue number7
DOIs
StatePublished - Apr 1 2008

Fingerprint

Epithelial Cells
Phenotype
Stem Cells
Liver
Fetal Stem Cells
Gene Expression
Endoderm
Bone Morphogenetic Proteins
Fibroblast Growth Factors
Transforming Growth Factors
Cell- and Tissue-Based Therapy
Cell Differentiation
Hepatocytes
Homeostasis
Transcription Factors
Cytokines

Keywords

  • Differentiation
  • Epithelial
  • Fetal
  • Liver
  • Mesenchymal
  • Stem cells

ASJC Scopus subject areas

  • Cell Biology

Cite this

Phenotype reversion in fetal human liver epithelial cells identifies the role of an intermediate meso-endodermal stage before hepatic maturation. / Inada, Mari; Follenzi, Antonia; Cheng, Kang; Surana, Manju; Joseph, Brigid; Benten, Daniel; Bandi, Sriram; Qian, Hong; Gupta, Sanjeev.

In: Journal of Cell Science, Vol. 121, No. 7, 01.04.2008, p. 1002-1013.

Research output: Contribution to journalArticle

Inada, Mari ; Follenzi, Antonia ; Cheng, Kang ; Surana, Manju ; Joseph, Brigid ; Benten, Daniel ; Bandi, Sriram ; Qian, Hong ; Gupta, Sanjeev. / Phenotype reversion in fetal human liver epithelial cells identifies the role of an intermediate meso-endodermal stage before hepatic maturation. In: Journal of Cell Science. 2008 ; Vol. 121, No. 7. pp. 1002-1013.
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