--- res: bibo_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.@eng bibo_authorlist: - foaf_Person: foaf_givenName: Philipp foaf_name: Velicky, Philipp foaf_surname: Velicky foaf_workInfoHomepage: http://www.librecat.org/personId=39BDC62C-F248-11E8-B48F-1D18A9856A87 orcid: 0000-0002-2340-7431 - foaf_Person: foaf_givenName: Gudrun foaf_name: Meinhardt, Gudrun foaf_surname: Meinhardt - foaf_Person: foaf_givenName: Kerstin foaf_name: Plessl, Kerstin foaf_surname: Plessl - foaf_Person: foaf_givenName: Sigrid foaf_name: Vondra, Sigrid foaf_surname: Vondra - foaf_Person: foaf_givenName: Tamara foaf_name: Weiss, Tamara foaf_surname: Weiss - foaf_Person: foaf_givenName: Peter foaf_name: Haslinger, Peter foaf_surname: Haslinger - foaf_Person: foaf_givenName: Thomas foaf_name: Lendl, Thomas foaf_surname: Lendl - foaf_Person: foaf_givenName: Karin foaf_name: Aumayr, Karin foaf_surname: Aumayr - foaf_Person: foaf_givenName: Mario foaf_name: Mairhofer, Mario foaf_surname: Mairhofer - foaf_Person: foaf_givenName: Xiaowei foaf_name: Zhu, Xiaowei foaf_surname: Zhu - foaf_Person: foaf_givenName: Birgit foaf_name: Schütz, Birgit foaf_surname: Schütz - foaf_Person: foaf_givenName: Roberta L. foaf_name: Hannibal, Roberta L. foaf_surname: Hannibal - foaf_Person: foaf_givenName: Robert foaf_name: Lindau, Robert foaf_surname: Lindau - foaf_Person: foaf_givenName: Beatrix foaf_name: Weil, Beatrix foaf_surname: Weil - foaf_Person: foaf_givenName: Jan foaf_name: Ernerudh, Jan foaf_surname: Ernerudh - foaf_Person: foaf_givenName: Jürgen foaf_name: Neesen, Jürgen foaf_surname: Neesen - foaf_Person: foaf_givenName: Gerda foaf_name: Egger, Gerda foaf_surname: Egger - foaf_Person: foaf_givenName: Mario foaf_name: Mikula, Mario foaf_surname: Mikula - foaf_Person: foaf_givenName: Clemens foaf_name: Röhrl, Clemens foaf_surname: Röhrl - foaf_Person: foaf_givenName: Alexander E. foaf_name: Urban, Alexander E. foaf_surname: Urban - foaf_Person: foaf_givenName: Julie foaf_name: Baker, Julie foaf_surname: Baker - foaf_Person: foaf_givenName: Martin foaf_name: Knöfler, Martin foaf_surname: Knöfler - foaf_Person: foaf_givenName: Jürgen foaf_name: Pollheimer, Jürgen foaf_surname: Pollheimer bibo_doi: 10.1371/journal.pgen.1007698 bibo_issue: '10' bibo_volume: 14 dct_date: 2018^xs_gYear dct_identifier: - UT:000449328500025 dct_isPartOf: - http://id.crossref.org/issn/1553-7404 dct_language: eng dct_publisher: Public Library of Science@ dct_title: Genome amplification and cellular senescence are hallmarks of human placenta development@ ...