How does nanog expression change during differentiation of embryonic stem cells?
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Changes in Nanog Expression During Differentiation of Embryonic Stem Cells
Introduction to Nanog and Pluripotency
Nanog is a critical transcription factor that plays a central role in maintaining the pluripotency of embryonic stem cells (ESCs). It is part of a core network of transcription factors, including Oct4 and Sox2, that sustain the self-renewal and undifferentiated state of ESCs . Understanding how Nanog expression changes during differentiation is essential for insights into stem cell biology and potential therapeutic applications.
Fluctuations in Nanog Expression
Temporal Fluctuations and Cell Fate Decisions
Nanog expression in ESCs is not static; it exhibits temporal fluctuations that are crucial for cell fate decisions. These fluctuations allow a pluripotent cell population to comprise cells at different stages of readiness for differentiation. This dynamic expression pattern suggests that Nanog levels can influence whether a cell remains pluripotent or begins to differentiate.
Heterogeneous Expression Patterns
Nanog expression is heterogeneous among ESCs, meaning that different cells within the same population can have varying levels of Nanog. This heterogeneity is influenced by factors such as microRNAs, specifically mir-296, which can fine-tune Nanog expression to regulate ESC proliferation and differentiation along specific lineages. The variability in Nanog expression is a functional element that controls the differentiation propensity of ESCs.
Regulation of Nanog During Differentiation
Downregulation and Differentiation
As ESCs begin to differentiate, Nanog expression is typically downregulated. This downregulation is associated with chromatin decondensation and nuclear softening, which are preparatory steps for lineage commitment. The transient downregulation of Nanog predisposes cells towards differentiation but does not necessarily mark a commitment to a specific lineage.
Role of Signaling Pathways
Signaling pathways also play a significant role in regulating Nanog during differentiation. For instance, FGF2 signaling through the MEK-ERK pathway can prolong Nanog expression during BMP4-induced differentiation, thereby influencing the lineage outcome of human ESCs. This pathway helps maintain Nanog levels, which is crucial for directing cells towards specific differentiation pathways.
Genetic and Epigenetic Influences
Allelic Regulation and Genetic Background
Nanog expression is biallelic and exhibits variability similar to other pluripotency factors. The genetic background and gene-targeting strategies used in studies can significantly influence the observed expression patterns of Nanog. This suggests that both genetic and epigenetic factors are critical in regulating Nanog expression during ESC differentiation.
Role of Satb Proteins
Satb1 and Satb2 proteins are involved in regulating Nanog expression and higher-order chromatin structure. Satb1-deficient ESCs show impaired differentiation potential and increased Nanog expression, indicating that these proteins play a role in balancing Nanog levels to facilitate proper differentiation.
Conclusion
Nanog expression in embryonic stem cells is a dynamic and tightly regulated process that plays a crucial role in maintaining pluripotency and guiding differentiation. Temporal fluctuations, heterogeneous expression patterns, and the influence of signaling pathways and genetic factors all contribute to the regulation of Nanog. Understanding these mechanisms provides valuable insights into stem cell biology and the potential for developing targeted therapies for regenerative medicine.
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