Spatial patterning of liver progenitor cell differentiation mediated by cellular contractility and Notch signaling
Spatial patterning of liver progenitor cell differentiation mediated by cellular contractility and Notch signaling
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DOI：
10.7554/elife.38536
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发表时间：
2018-12-27
期刊：
影响因子：
7.7
通讯作者：
Underhill, Gregory H.
中科院分区：
文献类型：
--
作者：
Kaylan, Kerim B.;Berg, Ian C.;Underhill, Gregory H.
The progenitor cells of the developing liver can differentiate toward both hepatocyte and biliary cell fates. In addition to the established roles of TGFb and Notch signaling in this fate specification process, there is increasing evidence that liver progenitors are sensitive to mechanical cues. Here, we utilized microarrayed patterns to provide a controlled biochemical and biomechanical microenvironment for mouse liver progenitor cell differentiation. In these defined circular geometries, we observed biliary differentiation at the periphery and hepatocytic differentiation in the center. Parallel measurements obtained by traction force microscopy showed substantial stresses at the periphery, coincident with maximal biliary differentiation. We investigated the impact of downstream signaling, showing that peripheral biliary differentiation is dependent not only on Notch and TGFb but also E-cadherin, myosin-mediated cell contractility, and ERK. We have therefore identified distinct combinations of microenvironmental cues which guide fate specification of mouse liver progenitors toward both hepatocyte and biliary fates.
