| First Author | Garibaldi F | Year | 2012 |
| Journal | Cell Death Differ | Volume | 19 |
| Issue | 6 | Pages | 937-46 |
| PubMed ID | 22139130 | Mgi Jnum | J:203611 |
| Mgi Id | MGI:5527524 | Doi | 10.1038/cdd.2011.175 |
| Citation | Garibaldi F, et al. (2012) An epistatic mini-circuitry between the transcription factors Snail and HNF4alpha controls liver stem cell and hepatocyte features exhorting opposite regulation on stemness-inhibiting microRNAs. Cell Death Differ 19(6):937-46 |
| abstractText | 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 HNF4alpha, directly represses the expression of the epithelial microRNAs (miRs)-200c and -34a, which in turn target several stem cell genes. Notably, in differentiated hepatocytes HNF4alpha, 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, HNF4alpha and miRs-200a, b, c and -34a as epistatic elements controlling hepatic stem cell maintenance/differentiation. |
