Reactivation of embryonic genetic programs in tissue regeneration and disease

Embryonic genetic programs are reactivated in response to various types of tissue damage, providing cell plasticity for tissue regeneration or disease progression. In acute conditions, these programs remedy the damage and then halt to allow a return to homeostasis. In chronic situations, including inflammatory diseases, fibrosis and cancer, prolonged activation of embryonic programs leads to disease progression and tissue deterioration. Induction of progenitor identity and cell plasticity, for example, epithelial-mesenchymal plasticity, are critical outcomes of reactivated embryonic programs. In this Review, we describe molecular players governing reactivated embryonic genetic programs, their role during disease progression, their similarities and differences and lineage reversion in pathology and discuss associated therapeutics and drug-resistance mechanisms across many organs. We also discuss the diversity of reactivated programs in different disease contexts. A comprehensive overview of commonalities between development and disease will provide better understanding of the biology and therapeutic strategies.