Aloia, L;
McKie, MA;
Vernaz, G;
Cordero-Espinoza, L;
Aleksieva, N;
van den Ameele, J;
Antonica, F;
... Huch, M; + view all
(2019)
Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration.
Nature Cell Biology
, 21
(11)
pp. 1321-1333.
10.1038/s41556-019-0402-6.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41556-019-0402-6 |
| Publisher version: | https://doi.org/10.1038/s41556-019-0402-6 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10097378 |
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