Department of Molecular Life Sciences, University of Zürich, Zürich, Switzerland.
Nat Genet. 2023 Nov;55(11):1792-1806. doi: 10.1038/s41588-023-01526-4. Epub 2023 Oct 30.
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.
胚胎遗传程序会被各种类型的组织损伤激活，为组织再生或疾病进展提供细胞可塑性。在急性情况下，这些程序会修复损伤，然后停止以恢复体内平衡。在慢性情况下，包括炎症性疾病、纤维化和癌症，胚胎程序的长期激活会导致疾病进展和组织恶化。诱导祖细胞特性和细胞可塑性，例如上皮-间充质可塑性，是重新激活的胚胎程序的关键结果。在这篇综述中，我们描述了控制重新激活的胚胎遗传程序的分子参与者，它们在疾病进展过程中的作用，它们的相似性和差异性，以及在病理学中的谱系逆转，并讨论了许多器官中的相关治疗方法和耐药机制。我们还讨论了不同疾病背景下重新激活程序的多样性。对发育和疾病之间共同点的全面了解将有助于更好地理解生物学和治疗策略。
