祖细胞
Notch信号通路
细胞生物学
生物
细胞命运测定
细胞分化
肝细胞
祖细胞
斑马鱼
干细胞
信号转导
遗传学
基因
转录因子
体外
作者
Kerim B. Kaylan,Ian C. Berg,Matthew J. Biehl,Aidan Brougham-Cook,Ishita Jain,Sameed M Jamil,Lauren H Sargeant,Nicholas J Cornell,Lori T. Raetzman,Gregory H. Underhill
出处
期刊:eLife
[eLife Sciences Publications, Ltd.]
日期:2018-12-27
卷期号:7
被引量:35
摘要
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.
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