TY - JOUR
T1 - 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
AU - Conigliaro, Alice
AU - Conigliaro, Alice
AU - Cozzolino, Angela M.
AU - Santangelo, Laura
AU - Grassi, null
AU - Garibaldi, null
AU - Amicone, Laura
AU - Cicchini, Carla
AU - Tripodi, Marco
AU - Marchetti, null
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Genetic; Cell Biology; Molecular Biology
KW - Hepatocyte differentiation; HNF4a; MiR-34a; MiRs-200; Snail; Stemness; Animals; Cell Differentiation; Epithelial-Mesenchymal Transition; Hepatocyte Nuclear Factor 4; Hepatocytes; Liver; Mice; Mice
KW - Knockout; MicroRNAs; Snail Family Transcription Factors; Stem Cells; Transcription Factors; Transcription
KW - Genetic; Cell Biology; Molecular Biology
KW - Hepatocyte differentiation; HNF4a; MiR-34a; MiRs-200; Snail; Stemness; Animals; Cell Differentiation; Epithelial-Mesenchymal Transition; Hepatocyte Nuclear Factor 4; Hepatocytes; Liver; Mice; Mice
KW - Knockout; MicroRNAs; Snail Family Transcription Factors; Stem Cells; Transcription Factors; Transcription
UR - http://hdl.handle.net/10447/241681
M3 - Article
VL - 19
SP - 937
EP - 946
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
SN - 1350-9047
ER -