Abstract:
:The progenitor cells of the developing liver can differentiate toward both hepatocyte and biliary cell fates. In addition to the established roles of TGFβ 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 TGFβ 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.
journal_name
Elifejournal_title
eLifeauthors
Kaylan KB,Berg IC,Biehl MJ,Brougham-Cook A,Jain I,Jamil SM,Sargeant LH,Cornell NJ,Raetzman LT,Underhill GHdoi
10.7554/eLife.38536subject
Has Abstractpub_date
2018-12-27 00:00:00issn
2050-084Xpii
38536journal_volume
7pub_type
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