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Efficient Differentiation of Pluripotent Stem Cells to NKX6-1+ Pancreatic Progenitors
Published on: March 7, 2017
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p120ctn-Mediated Organ Patterning Precedes and Determines Pancreatic Progenitor Fate
Pia Nyeng1, Silja Heilmann1, Zarah M Löf-Öhlin1
1Novo Nordisk Foundation Center for Stem Cell Biology (Danstem), University of Copenhagen, 2200 Copenhagen N, Denmark.
Developmental Cell
|March 12, 2019
Summary
Pancreatic progenitor cells reposition themselves to establish niches that dictate their fate, guided by p120catenin. This cellular positioning mechanism coordinates organ shape and cell type specification during development.
Area of Science:
- Developmental Biology
- Cell Biology
- Organogenesis
Background:
- The mechanisms underlying organ shape emergence and cell fate specification remain largely unknown.
- Pancreatic duct, endocrine, and acinar lineages arise in distinct spatial domains.
- The pre-determination versus niche-settlement models for lineage specification are debated.
Purpose of the Study:
- To reconcile opposing models of lineage determination in the pancreas.
- To elucidate the mechanism coordinating organ architecture and cell fate specification.
- To identify the molecular players involved in pancreatic progenitor cell positioning.
Main Methods:
- Investigated the role of p120catenin (p120ctn) in pancreatic progenitor cell behavior.
- Analyzed differential E-cadherin-based cell sorting.
- Examined progenitor re-localization and subsequent cell fate acquisition.
Main Results:
- Demonstrated that pancreatic progenitors re-localize to establish niches that determine their fate.
- Identified a p120ctn-regulated mechanism coordinating organ architecture and cell fate via cell sorting.
- Showed reduced p120ctn expression causes progenitor re-localization to the tip domain, leading to acinar fate acquisition.
- Revealed this mechanism is re-iteratively used in endocrine specification, balancing alpha and beta cell fate choice.
Conclusions:
- Organ patterning is regulated by p120catenin-mediated cellular positioning.
- Cellular positioning precedes and determines pancreatic progenitor cell fate.
- This mechanism is crucial for both initial lineage segregation and subsequent cell fate decisions.
Keywords:
CTNND1beta cellcell segregationdevelopmentdifferentiationnichep120ctnpancreaspatterningprogenitorMore Related Videos
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