An epistatic mini-circuitry between the transcription factors Snail and HNF4α controls liver stem cell and hepatocyte features exhorting opposite regulation on stemness-inhibiting microRNAs

F. Garibaldi, C. Cicchini, A. Conigliaro, L. Santangelo, A. M. Cozzolino, G. Grassi, A. Marchetti, M. Tripodi, L. Amicone

Research output: Contribution to journalArticlepeer-review

Abstract

Preservation of the epithelial state involves the stable repression of epithelial-to-mesenchymal transition program, whereas maintenance of the stem compartment requires the inhibition of differentiation processes. A simple and direct molecular mini-circuitry between master elements of these biological processes might provide the best device to keep balanced such complex phenomena. In this work, we show that in hepatic stem cell Snail, a transcriptional repressor of the hepatocyte differentiation master gene HNF4α, directly represses the expression of the epithelial microRNAs (miRs)-200c and-34a, which in turn target several stem cell genes. Notably, in differentiated hepatocytes HNF4α, previously identified as a transcriptional repressor of Snail, induces the miRs-34a and-200a, b, c that, when silenced, causes epithelial dedifferentiation and reacquisition of stem traits. Altogether these data unveiled Snail, HNF4α and miRs-200a, b, c and-34a as epistatic elements controlling hepatic stem cell maintenance/differentiation.

Original languageEnglish
Pages (from-to)937-946
Number of pages10
JournalCell Death and Differentiation
Volume19
Issue number6
DOIs
Publication statusPublished - Jun 2012

Keywords

  • Hepatocyte differentiation
  • HNF4a
  • MiR-34a
  • MiRs-200
  • Snail
  • Stemness

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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