Adult tissue derived organoid cultures and their application to the understanding of tissue regeneration and cancer

Datum

01.04.2021

Zeit

11:00 - 12:00

Sprecher

Meritxell Huch

Zugehörigkeit

MPI-CBG Dresden

Serie

MPI-CBG Thursday Seminar

Sprache

en

Hauptthema

Biologie

Host

Anne Grapin-Botton

Beschreibung

In vitro 3D cultures are emerging as novel systems to study tissue development, organogenesis and stem cell behavior ex-vivo. My lab and I, we have developed organoid cultures from healthy and diseased, human and mouse, adult and embryonic tissues for a range of organs including stomach, liver and pancreas. These have allowed, for the first time, the long-term expansion of adult (stomach, liver and pancreas) and embryonic (liver) tissue into 3D-epithelial structures that we have termed organoids, since these (1) self-assemble and can be clonally expanded, (2) resemble the corresponding tissues-of-origin and (3) allow the study of some aspects of tissue physiology in a dish. Here, I will present our liver organoid work and summarize our findings that our organoid culture system recapitulates many aspects of liver regeneration in a dish, specially the activation of adult differentiated liver cells into proliferating progenitors. At the molecular scale, we have found that progenitor activation from differentiated cells occurs through a transient, genome-wide remodelling, of the cells’ transcriptome and epigenome (DNA methylome/ hydroxymethylome), both during organoid initiation and in vivo, following tissue damage. At the tissue scale, absence of this epigenetic remodeling results in loss of regenerative potential and fibrosis. Our results argue in favour of the remodelling of genomic methylome/hydroxymethylome landscapes as a more general mechanism by which differentiated cells exit a committed state in response to damage and initiate the regenerative response.

Letztmalig verändert: 02.04.2021, 00:10:41