Abstract
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.
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Acknowledgements
We thank E. Brunner and T. Dalessi for discussions as well as other members of the Basler laboratory including M. D. Brügger, G. Hausmann, T. Valenta, D. King, G. Moro, A. F. Guthörl and L. F. Rago for critical input on the manuscript. Considering the broad topic of this Review and limited space, we were not able to include all essential studies and therefore apologize to authors whose work we did not cite. H.F. was supported by the Forschungskredit of the University of Zürich (grant FK-21-119) and a grant from the University and Medical Faculty of Zürich and the Comprehensive Cancer Center Zürich. K.B. is supported by Swiss National Science Foundation (grants 192475 and 207594) project funding in biology and medicine.
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Fazilaty, H., Basler, K. Reactivation of embryonic genetic programs in tissue regeneration and disease. Nat Genet 55, 1792–1806 (2023). https://doi.org/10.1038/s41588-023-01526-4
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DOI: https://doi.org/10.1038/s41588-023-01526-4