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 HNF4Î±, directly represses the expression of the epithelial microRNAs (miRs)-200c and-34a, which in turn target several stem cell genes. Notably, in differentiated hepatocytes HNF4Î±, 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, HNF4Î± and miRs-200a, b, c and-34a as epistatic elements controlling hepatic stem cell maintenance/differentiation. Â© 2012 Macmillan Publishers Limited. All rights reserved.
|Numero di pagine||10|
|Rivista||Cell Death and Differentiation|
|Stato di pubblicazione||Published - 2012|
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology