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RESEARCH PRODUCT
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
Alessandra MarchettiMarco TripodiF GaribaldiLaura AmiconeCarla CicchiniAlice ConigliaroG GrassiAngela Maria CozzolinoLaura Santangelosubject
Transcription GeneticTranscription FactorCellular differentiationLiver Stem CellSnailMESH: Mice KnockoutMESH: HepatocytesMice0302 clinical medicineSnail; hnf4a; mir-200; mir-34a; stemness; hepatocyte differentiationHepatocyteMESH: AnimalsMice KnockoutHepatocyte differentiationmir-34a0303 health sciencesStemneStem CellsMicroRNACell DifferentiationMESH: Transcription FactorsCell biologySnailmir-200Hepatocyte Nuclear Factor 4Liver030220 oncology & carcinogenesisMiRs-200MESH: Hepatocyte Nuclear Factor 4Hepatocyte differentiation; HNF4a; MiR-34a; MiRs-200; Snail; Stemness; Animals; Cell Differentiation; Epithelial-Mesenchymal Transition; Hepatocyte Nuclear Factor 4; Hepatocytes; Liver; Mice; Mice Knockout; MicroRNAs; Snail Family Transcription Factors; Stem Cells; Transcription Factors; Transcription Genetic; Cell Biology; Molecular BiologyStem cellhnf4aMESH: Cell Differentiationhepatocyte differentiationEpithelial-Mesenchymal TransitionMESH: Stem Cells[SDV.BC]Life Sciences [q-bio]/Cellular BiologyBiologystemness03 medical and health sciencesStem Cellbiology.animalAnimals[SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular BiologyEpithelial–mesenchymal transitionMESH: MiceMolecular BiologyTranscription factor030304 developmental biologyOriginal PaperAnimalMESH: Transcription GeneticSnail Family Transcription FactorCell BiologyMolecular biologyMicroRNAsMESH: Epithelial-Mesenchymal TransitionHepatocyte nuclear factor 4HepatocytesSnail Family Transcription FactorsMESH: MicroRNAsMESH: LiverTranscription Factorsdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2011-12-02 | Cell Death & Differentiation |