ArticlePLoS genetics2018
Genome amplification and cellular senescence are hallmarks of human placenta development.
Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.
- Revealing the molecular landscape of human placenta: a systematic review and meta-analysis of single-cell RNA sequencing studies.Human reproduction update · 2024Pooled it
- Immunological consequences of senescence in physiology and pathology.Journal of translational medicine · 2026Review
- Advantages, limitations, and innovative considerations for established and emerging models of human placental syncytiotrophoblast.Human reproduction update · 2026Review
- Chronic replication stress-mediated genomic instability disrupts placenta development in mice.PLoS genetics · 2026Article
- Integrative bioinformatics analysis identifies placental senescence-associated signatures in early-onset preeclampsia.Frontiers in endocrinology · 2026Article
- METTL3 safeguards cell identity and epigenome of human trophoblast stem cells.Nature communications · 2025Article
- The human placenta and its role in reproductive outcomes revisited.Physiological reviews · 2025Review
- The dual role of whole-genome duplication: biological mechanisms, functional consequences, and detection advances.Acta biochimica et biophysica Sinica · 2025Review
- Cells of the Maternal-Fetal Interface May Contribute to Epidural-Related Maternal Fever After Administration of Ropivacaine: The Role of Phosphatases DUSP9 and PHLPP1.International journal of molecular sciences · 2025Article
- HSD17B1-mediated trophoblast differentiation lowers estrogen levels in early-onset preeclampsia.Scientific reports · 2025Article
- Epidermal growth factor receptor in placental health and disease: pathways, dysfunction, and chemical disruption.Toxicological sciences : an official journal of the Society of Toxicology · 2025Review
- The multifaceted roles of the transcriptional coactivator TAZ in extravillous trophoblast development of the human placenta.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Role of vitamin D in the pathogenesis of early-onset preeclampsia: a narrative review.Frontiers in nutrition · 2025Review
- SenNet recommendations for detecting senescent cells in different tissues.Nature reviews. Molecular cell biology · 2024Review
- The Last Universal Common Ancestor of Ribosome-Encoding Organisms: Portrait of LUCA.Journal of molecular evolution · 2024Review
- Article
- Functional consequences of somatic polyploidy in development.Development (Cambridge, England) · 2024Review
- Research Progress on Extracellular Matrix Involved in the Development of Preeclampsia.Current protein & peptide science · 2024Review
- Linking DNA damage and senescence to gestation period and lifespan in placental mammals.Frontiers in cell and developmental biology · 2024Article
Corrections and comments
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Authors and funding
23 authors at 5 institutions in 3 countries.
Funding
Abstract
Genome amplification and cellular senescence are commonly associated with pathological processes. While physiological roles for polyploidization and senescence have been described in mouse development, controversy exists over their significance in humans. Here, we describe tetraploidization and senescence as phenomena of normal human placenta development. During pregnancy, placental extravillous trophoblasts (EVTs) invade the pregnant endometrium, termed decidua, to establish an adapted microenvironment required for the developing embryo. This process is critically dependent on continuous cell proliferation and differentiation, which is thought to follow the classical model of cell cycle arrest prior to terminal differentiation. Strikingly, flow cytometry and DNAseq revealed that EVT formation is accompanied with a genome-wide polyploidization, independent of mitotic cycles. DNA replication in these cells was analysed by a fluorescent cell-cycle indicator reporter system, cell cycle marker expression and EdU incorporation. Upon invasion into the decidua, EVTs widely lose their replicative potential and enter a senescent state characterized by high senescence-associated (SA) β-galactosidase activity, induction of a SA secretory phenotype as well as typical metabolic alterations. Furthermore, we show that the shift from endocycle-dependent genome amplification to growth arrest is disturbed in androgenic complete hydatidiform moles (CHM), a hyperplastic pregnancy disorder associated with increased risk of developing choriocarinoma. Senescence is decreased in CHM-EVTs, accompanied by exacerbated endoreduplication and hyperploidy. We propose induction of cellular senescence as a ploidy-limiting mechanism during normal human placentation and unravel a link between excessive polyploidization and reduced senescence in CHM.
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Registered trials
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