This paper details research into the mechanisms governing cellular plasticity in thymic epithelial cells (mTECs), which is essential for immune tolerance. The authors demonstrate that fluctuations in background chromatin accessibility, termed "epigenetic noise," are amplified during mTEC maturation and promote the ectopic expression of genes normally restricted to other cell types. Crucially, this epigenetic noise is associated with the repression of the tumor suppressor p53; conversely, augmenting p53 activity stabilizes chromatin, suppresses ectopic gene expression, and restricts cellular plasticity, leading to multi-organ autoimmunity in mice. The study also links this noise to genomically encoded AT-rich sequences and suggests a similar regulatory role for p53 in suppressing plasticity during lung adenocarcinoma progression.

References:

• Gamble N, Caldwell J A, McKeever J, et al. Thymic epithelial cells amplify epigenetic noise to promote immune tolerance[J]. Nature, 2025: 1-10.