Spatial patterning of liver progenitor cell differentiation mediated by cellular contractility and Notch signaling.

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

Elife

journal_title

eLife

authors

Kaylan KB,Berg IC,Biehl MJ,Brougham-Cook A,Jain I,Jamil SM,Sargeant LH,Cornell NJ,Raetzman LT,Underhill GH

doi

10.7554/eLife.38536

subject

Has Abstract

pub_date

2018-12-27 00:00:00

issn

2050-084X

pii

38536

journal_volume

7

pub_type

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