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Cytoplasmic and Nuclear TAZ Exert Distinct Functions in Regulating Primed Pluripotency
Xingliang Zhou1, Jean Paul Chadarevian1, Bryan Ruiz1
1Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Stem Cell Reports
|August 29, 2017
Summary
Cytoplasmic beta-catenin retains TAZ, promoting self-renewal in primed stem cells. Nuclear TAZ induces differentiation, revealing TAZ
Area of Science:
- Stem cell biology
- Cell signaling
- Developmental biology
Background:
- Primed pluripotent stem cells like mouse epiblast stem cells (mEpiSCs) and human embryonic stem cells (hESCs) require specific conditions for self-renewal.
- The precise molecular mechanisms maintaining self-renewal in these primed states, particularly involving beta-catenin and TAZ, are not fully understood.
Purpose of the Study:
- To elucidate the role of cytoplasmic beta-catenin and its interaction with TAZ in maintaining the self-renewal of primed pluripotent stem cells.
- To investigate how the subcellular localization of TAZ influences cell fate decisions in different stem cell types.
Main Methods:
- Co-immunoprecipitation assays to detect protein interactions.
- Immunofluorescence microscopy to determine subcellular localization of beta-catenin and TAZ.
- Cell culture experiments manipulating beta-catenin and TAZ localization.
- Analysis of stem cell self-renewal and differentiation markers.
Main Results:
- Cytoplasmic beta-catenin directly interacts with and retains TAZ in the cytoplasm.
- Cytoplasmic TAZ promotes mEpiSC self-renewal, while nuclear TAZ triggers differentiation.
- TAZ is not essential for naive mouse embryonic stem cell (mESC) self-renewal but is crucial for mESC to mEpiSC conversion.
- Similar mechanisms involving cytoplasmic beta-catenin and TAZ retention are observed in hESC self-renewal.
Conclusions:
- The subcellular localization of TAZ is a critical determinant of cell fate in pluripotent stem cells.
- Cytoplasmic retention of TAZ, mediated by beta-catenin, is essential for maintaining the self-renewal of primed stem cells (mEpiSCs and hESCs).
- Understanding TAZ's localization-dependent function offers insights into stem cell regulation and differentiation pathways.
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