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Essential role of STAT3 for embryonic stem cell pluripotency
R Raz1, C K Lee, L A Cannizzaro
1Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
Summary
Leukemia inhibitory factor (LIF) is crucial for mouse embryonic stem (ES) cell self-renewal, acting through STAT3. Maintaining sufficient STAT3 activity is essential for undifferentiated ES cell growth.
Area of Science:
- Stem cell biology
- Molecular signaling pathways
Background:
- Mouse embryonic stem (ES) cells require leukemia inhibitory factor (LIF) for in vitro propagation.
- Leukemia inhibitory factor (LIF) signaling involves kinases and the signal transducer and transcriptional activator STAT3.
Purpose of the Study:
- To investigate the role of STAT3 in maintaining the undifferentiated phenotype of mouse embryonic stem (ES) cells during LIF withdrawal.
- To determine the correlation between STAT3 activity and ES cell self-renewal at clonal density.
Main Methods:
- Monitoring STAT3 activation and ES cell differentiation during LIF withdrawal.
- Targeted mutagenesis of the Stat3 gene in ES cell lines with varying LIF dependency.
- Utilizing Cre recombination for reversible Stat3 gene abrogation and copy number reduction.
Main Results:
- STAT3 activity positively correlates with the maintenance of an undifferentiated ES cell phenotype at clonal density.
- STAT3 activity levels do not impact ES cell proliferation rates.
- Dose-dependent reduction of STAT3 activity leads to decreased self-renewal efficiency without affecting cell cycle progression.
Conclusions:
- A critical level of STAT3 activity is essential for maintaining the undifferentiated state of mouse embryonic stem cells.
- STAT3 plays a crucial role in ES cell self-renewal, independent of its effect on proliferation.