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Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration.


Aloia L, McKie MA, Vernaz G, Cordero-Espinoza L, Aleksieva N, van den Ameele J, Antonica F, Font-Cunill B, Raven A, Aiese Cigliano R, Belenguer G, Mort RL, Brand AH, Zernicka-Goetz M, Forbes SJ, Miska EA, Huch M

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.

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Antibody
LowCell ChIP kit
IPure kit

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Published
November, 2019

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Products used in this publication

  • cut and tag antibody icon
    C15410003-50
    H3K4me3 Antibody - ChIP-seq Grade
  • ChIP kit icon
    C01010072
    LowCell# ChIP kit protein A
  • ChIP kit icon
    C01010073
    LowCell# ChIP kit protein G
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    C03010015
    IPure kit v2
  • default alt
    C03010020-220
    DiaMag protein A-coated magnetic beads (ChIP-se...
  • default alt
    C03010021-220
    DiaMag protein G-coated magnetic beads (ChIP-se...

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