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

First Author  Cordero-Espinoza L Year  2021
Journal  Cell Stem Cell Volume  28
Issue  11 Pages  1907-1921.e8
PubMed ID  34343491 Mgi Jnum  J:350345
Mgi Id  MGI:6874762 Doi  10.1016/j.stem.2021.07.002
Citation  Cordero-Espinoza L, et al. (2021) Dynamic cell contacts between periportal mesenchyme and ductal epithelium act as a rheostat for liver cell proliferation. Cell Stem Cell 28(11):1907-1921.e8
abstractText  In the liver, ductal cells rarely proliferate during homeostasis but do so transiently after tissue injury. These cells can be expanded as organoids that recapitulate several of the cell-autonomous mechanisms of regeneration but lack the stromal interactions of the native tissue. Here, using organoid co-cultures that recapitulate the ductal-to-mesenchymal cell architecture of the portal tract, we demonstrate that a subpopulation of mouse periportal mesenchymal cells exerts dual control on proliferation of the epithelium. Ductal cell proliferation is either induced and sustained or, conversely, completely abolished, depending on the number of direct mesenchymal cell contacts, through a mechanism mediated, at least in part, by Notch signaling. Our findings expand the concept of the cellular niche in epithelial tissues, whereby not only soluble factors but also cell-cell contacts are the key regulatory cues involved in the control of cellular behaviors, suggesting a critical role for cell-cell contacts during regeneration.
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