Dynamic cell contacts between periportal mesenchyme and ductal epithelium act as a rheostat for liver cell proliferation

• DOI: 10.1016/j.stem.2021.07.002
• Publication Date: 2021-08-02T14:32:19Z
• Authors: Lucía Cordero-Esp...; Anna M. Dowbaj; Timo N. Kohler; Bernhard Strauss; Olga Sarlidou; German Belenguer; Clare Pacini; Nuno P. Martins; Ross Dobie; John R. Wilson-Ka...; Richard Butler; Nicole Prior; Palle Serup; Florian Jug; Neil C. Henderson; Florian Hollfelder; Meritxell Huch
• Keywords: Mesenchyme; Organoid; Cell type

In the liver, ductal cells rarely proliferate during homeostasis but do so transiently after tissue injury. These can be expanded as organoids that recapitulate several of cell-autonomous mechanisms regeneration lack stromal interactions native tissue. Here, using organoid co-cultures ductal-to-mesenchymal cell architecture portal tract, we demonstrate a subpopulation mouse periportal mesenchymal exerts dual control on proliferation epithelium. Ductal is either induced and sustained or, conversely, completely abolished, depending number direct contacts, through mechanism mediated, at least in part, by Notch signaling. Our findings expand concept cellular niche epithelial tissues, whereby not only soluble factors also cell-cell contacts are key regulatory cues involved behaviors, suggesting critical role for regeneration.