Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration

Article:

Luigi Aloia, Mikel Alexander McKie, Grégoire Vernaz, Lucía Cordero-Espinoza, Niya Aleksieva, Jelle van den Ameele, Francesco Antonica, Berta Font-Cunill, Alexander Raven, Riccardo Aiese Cigliano, German Belenguer, Richard L Mort, Andrea H Brand, Magdalena Zernicka-Goetz, Stuart J Forbes, Eric A Miska, Meritxell Huch

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.

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