Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration
| Autor: | Riccardo Aiese Cigliano, German Belenguer, Stuart J. Forbes, Francesco Antonica, Magdalena Zernicka-Goetz, Lucía Cordero-Espinoza, Richard L. Mort, Eric A. Miska, Mikel A. McKie, Niya Aleksieva, Grégoire Vernaz, Andrea H. Brand, Luigi Aloia, Berta Font-Cunill, Meritxell Huch, Jelle van den Ameele, Alexander Raven |
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| Přispěvatelé: | Aloia, Luigi [0000-0003-4509-2730], McKie, Mikel Alexander [0000-0002-1711-4034], Vernaz, Grégoire [0000-0001-8942-2370], van den Ameele, Jelle [0000-0002-2744-0810], Antonica, Francesco [0000-0001-9359-9689], Zernicka-Goetz, Magdalena [0000-0002-7004-2471], Forbes, Stuart J [0000-0003-3715-2561], Miska, Eric A [0000-0002-4450-576X], Huch, Meritxell [0000-0002-1545-5265], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
Ductal cells Liver cytology Cellular differentiation Primary Cell Culture Cell Cycle Proteins Mice Transgenic Biology Protein Serine-Threonine Kinases Article Epigenesis Genetic Transcriptome 03 medical and health sciences Epigenome 0302 clinical medicine Proto-Oncogene Proteins Organoid Animals Hippo Signaling Pathway 030304 developmental biology Adaptor Proteins Signal Transducing 0303 health sciences Regeneration (biology) Gene Expression Profiling Epithelial Cells YAP-Signaling Proteins Cell Biology DNA Methylation Liver regeneration Cell biology Liver Regeneration DNA-Binding Proteins Organoids Liver 030220 oncology & carcinogenesis Female Bile Ducts Signal Transduction |
| Zdroj: | Aloia, L, Mckie, M A, Vernaz, G, Cordero-Espinoza, L, Aleksieva, N, van den Ameele, J, Antonica, F, Font-Cunill, B, Raven, A, Cigliano, R A, Belenguer, G, Mort, R L, Brand, A H, Zernicka-Goetz, M, Forbes, S J, Miska, E A & Huch, M 2019, ' Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration ', Nature Cell Biology, vol. 21, no. 11, pp. 1321–1333 . https://doi.org/10.1038/s41556-019-0402-6 Nat Cell Biol |
| DOI: | 10.1038/s41556-019-0402-6 |
| Popis: | Following severe or chronic liver injury, adult ductal cells (cholangiocytes) contribute to regeneration by restoring both hepatocytes and cholangiocytes. We recently showed that ductal cells clonally expand as self-renewing liver organoids that retain their differentiation capacity into both hepatocytes and ductal cells. However, the molecular mechanisms by which adult ductal-committed cells acquire cellular plasticity, initiate organoids and regenerate the damaged tissue remain largely unknown. Here, we describe that ductal cells undergo a transient, genome-wide, remodelling of their transcriptome and epigenome during organoid initiation and in vivo following tissue damage. TET1-mediated hydroxymethylation licences differentiated ductal cells to initiate organoids and activate the regenerative programme through the transcriptional regulation of stem-cell genes and regenerative pathways including the YAP-Hippo signalling. Our results argue in favour of the remodelling of genomic methylome/hydroxymethylome landscapes as a general mechanism by which differentiated cells exit a committed state in response to tissue damage. |
| Databáze: | OpenAIRE |
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