Genome amplification and cellular senescence are hallmarks of human placenta development

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

63 Scopus Citations
View graph of relations

Author(s)

  • Philipp Velicky
  • Gudrun Meinhardt
  • Kerstin Plessl
  • Sigrid Vondra
  • Tamara Weiss
  • Peter Haslinger
  • Thomas Lendl
  • Karin Aumayr
  • Mario Mairhofer
  • Birgit Schütz
  • Roberta L. Hannibal
  • Robert Lindau
  • Beatrix Weil
  • Jan Ernerudh
  • Jürgen Neesen
  • Gerda Egger
  • Mario Mikula
  • Clemens Röhrl
  • Alexander E. Urban
  • Julie Baker
  • Martin Knöfler
  • Jürgen Pollheimer

Detail(s)

Original languageEnglish
Article numbere1007698
Journal / PublicationPLoS Genetics
Volume14
Issue number10
Publication statusPublished - 1 Oct 2018
Externally publishedYes

Link(s)

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.

Research Area(s)

Bibliographic Note

Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to [email protected].

Citation Format(s)

Genome amplification and cellular senescence are hallmarks of human placenta development. / Velicky, Philipp; Meinhardt, Gudrun; Plessl, Kerstin et al.
In: PLoS Genetics, Vol. 14, No. 10, e1007698, 01.10.2018.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

Download Statistics

No data available