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

Alice Conigliaro, Alice Conigliaro, Angela M. Cozzolino, Laura Santangelo, Grassi, Garibaldi, Laura Amicone, Carla Cicchini, Marco Tripodi, Marchetti

Risultato della ricerca: Articlepeer review

31 Citazioni (Scopus)

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. © 2012 Macmillan Publishers Limited. All rights reserved.
Lingua originaleEnglish
pagine (da-a)937-946
Numero di pagine10
RivistaCell Death and Differentiation
Volume19
Stato di pubblicazionePublished - 2012

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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