Spatial patterning of liver progenitor cell differentiation mediated by cell contractility and notch signaling

Conference Dates

June 5-9, 2018


Liver progenitor cell differentiation and bile duct formation are driven by spatially-dependent and temporally-sequenced cell–cell and cell–factor interactions coordinated by several biochemical signaling pathways, namely Notch and TGFβ. The regionalization of biliary differentiation and morphogenesis near the portal region of the liver has suggested that spatially segregated microenvironmental signals govern this process. Our recent work utilizing biomaterial substrates of defined stiffness suggests that mechanical cues play a previously-unrecognized role in liver progenitor differentiation. Here, we used a cell microarray platform that enables the simultaneous analysis of these biochemical and biomechanical microenvironmental cues to define the mechanisms of action and functional overlap of these pathways.

We used bipotential mouse embryonic liver (BMEL) progenitor cells cultured by standard techniques (M. Weiss and H. Strick-Marchand, Institut Pasteur). To present Notch ligand to cells, we printed Fc-chimeric recombinant DLL4 on a polyacrylamide hydrogel substrate together with collagen I and Protein A/G. We integrated this cell microarray platform with traction force microscopy (TFM) by adding fiducial beads to the polyacrylamide hydrogel and imaging bead displacement before and after cell dissociation.

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