How embryos pause growth in diapause ^{CEFR B2}

Many mammals use embryonic diapause to delay development until conditions improve; humans do not. A new paper in Genes & Development explores how diapaused mouse embryonic stem cells maintain their ability to become any cell type despite prolonged low metabolism or absent growth cues. Alexander Tarakhovsky and colleagues view diapause as a survival strategy that can be reached by different molecular routes.

The team compared several stressors that induce diapause-like states. Prior work showed that blocking mTOR, reducing Myc transcription factors, or altering chromatin regulators such as MOF push cells into low-energy modes. In the current study they used the BET inhibitor I-BET151 (which mimics Myc deficiency) and direct mTOR inhibition. In both conditions the cells lowered metabolism, RNA output and protein synthesis, resisted forced specialization, and—after removing inhibitors—could resume normal development and contribute to healthy embryos.

All stressors flipped the same core response: genes that act as brakes on the MAP kinase pathway were turned on. The researchers found that different stresses displaced the protein Capicua, which normally keeps those brake genes silent; losing Capicua allowed the brakes to engage and preserve pluripotency. Building on Tarakhovsky lab's epigenetic work including histone mimicry, the study argues that diapause arises from the structure of regulatory networks and suggests broader implications for immune cells, tissue stem cells, viruses, cancer cells, and possible effects on neuron aging and damage resistance.

• Shared molecular switch preserves cell identity.
• Different stresses use the same brake mechanism.
• Findings may explain long-term cell survival under stress.