Preservation of the epithelial state involves the stable repression of EMT program while 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, may 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 HNF4, directly represses the expression of the epithelial microRNAs-200c and -34a, which in turn target several stem cell genes. Notably, in differentiated hepatocytes HNF4, previously identified as a transcriptional repressor of Snail, induces the microRNAs-34a and -200a, b, c that, when silenced, causes epithelial dedifferentiation and reacquisition of stem traits. Altogether these data unveiled Snail, HNF4 and microRNAs -200a, b, c and -34a as epistatic elements controlling hepatic stem cell maintenance/differentiation.

An epistatic mini-circuitry between the transcription factors Snail and HNF4a controls liver stem cell and hepatocyte features exhorting opposite regulation on stemness-inhibiting microRNAs / Garibaldi, F.; Cicchini, Carla; Conigliaro, A.; Santangelo, L.; Cozzolino, A.; Grassi, G.; Marchetti, Alessandra; Tripodi, Marco; Amicone, Laura. - In: CELL DEATH AND DIFFERENTIATION. - ISSN 1350-9047. - STAMPA. - 19:6(2012), pp. 937-946. [10.1038/cdd.2011.175]

An epistatic mini-circuitry between the transcription factors Snail and HNF4a controls liver stem cell and hepatocyte features exhorting opposite regulation on stemness-inhibiting microRNAs

CICCHINI, Carla;MARCHETTI, ALESSANDRA;TRIPODI, Marco
;
AMICONE, Laura
2012

Abstract

Preservation of the epithelial state involves the stable repression of EMT program while 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, may 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 HNF4, directly represses the expression of the epithelial microRNAs-200c and -34a, which in turn target several stem cell genes. Notably, in differentiated hepatocytes HNF4, previously identified as a transcriptional repressor of Snail, induces the microRNAs-34a and -200a, b, c that, when silenced, causes epithelial dedifferentiation and reacquisition of stem traits. Altogether these data unveiled Snail, HNF4 and microRNAs -200a, b, c and -34a as epistatic elements controlling hepatic stem cell maintenance/differentiation.
2012
Snail; hnf4a; mir-200; mir-34a; stemness; hepatocyte differentiation
01 Pubblicazione su rivista::01a Articolo in rivista
An epistatic mini-circuitry between the transcription factors Snail and HNF4a controls liver stem cell and hepatocyte features exhorting opposite regulation on stemness-inhibiting microRNAs / Garibaldi, F.; Cicchini, Carla; Conigliaro, A.; Santangelo, L.; Cozzolino, A.; Grassi, G.; Marchetti, Alessandra; Tripodi, Marco; Amicone, Laura. - In: CELL DEATH AND DIFFERENTIATION. - ISSN 1350-9047. - STAMPA. - 19:6(2012), pp. 937-946. [10.1038/cdd.2011.175]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/424411
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