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Updated: Jan 9, 2026
Neural Differentiation of Mouse Embryonic Stem Cells in Serum-free Monolayer Culture
Published on: May 14, 2015
Stochastic NANOG fluctuations allow mouse embryonic stem cells to explore pluripotency
Elsa Abranches1, Ana M V Guedes2, Martin Moravec3
1Instituto de Medicina Molecular and Instituto de Histologia e Biologia do Desenvolvimento, Faculdade de Medicina da Universidade de Lisboa, Avenida Prof. Egas Moniz, Lisboa 1649-028, Portugal Champalimaud Neuroscience Programme, Champalimaud Centre for the Unknown, Avenida Brasilia - Doca de Pedrouços, Lisboa 1400-038, Portugal elsa.abranches@gmail.com henrique@fm.ul.pt.
Stochastic fluctuations in NANOG levels are inherent to mouse embryonic stem cells (mESCs), influencing their differentiation potential. Low NANOG states increase susceptibility to differentiation, while high NANOG states maintain pluripotency.
Area of Science:
- Stem cell biology
- Developmental biology
- Epigenetics
Background:
- Heterogeneous NANOG expression defines functional states in pluripotent stem cells.
- The origins and impact of NANOG expression fluctuations remain poorly understood.
Purpose of the Study:
- Investigate temporal dynamics of NANOG expression in mouse embryonic stem cells (mESCs).
- Dissect the lineage potential of mESCs across different NANOG expression states.
Main Methods:
- Utilized a novel fluorescent reporter for real-time NANOG monitoring in mESCs.
- Compared mESC behavior in standard and ground-state (2i) culture conditions.
- Analyzed lineage potential and gene expression profiles of low-NANOG vs. high-NANOG cells.
Main Results:
- Stochastic NANOG fluctuations are widespread in mESCs under both standard and ground-state conditions.
- NANOG fluctuations are inherent to the pluripotent state, with similar kinetics across conditions.
- Low-NANOG mESCs exhibit increased differentiation susceptibility and lineage-affiliated gene expression.
- High-NANOG mESCs maintain a stable expression profile with minimal lineage marker expression.
Conclusions:
- Stochastic NANOG fluctuations enable mESCs to explore diverse lineage options.
- NANOG dynamics modulate the probability of functional state transitions in pluripotent stem cells.
- This provides a mechanism for cellular plasticity within the pluripotent state.
