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Genome amplificatio...
Genome amplification and cellular senescence are hallmarks of human placenta development
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- Velicky, Philipp (author)
- Med Univ Vienna, Austria; IST Austria, Austria
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- Meinhardt, Gudrun (author)
- Med Univ Vienna, Austria
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- Plessl, Kerstin (author)
- Med Univ Vienna, Austria; Univ Appl Sci, Austria
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- Vondra, Sigrid (author)
- Med Univ Vienna, Austria
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- Weiss, Tamara (author)
- St Anna Childrens Hosp, Austria; Med Univ Vienna, Austria
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- Haslinger, Peter (author)
- Med Univ Vienna, Austria
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- Lendl, Thomas (author)
- Inst Mol Biotechnol, Austria; Gregor Mendel Inst, Austria
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- Aumayr, Karin (author)
- Inst Mol Biotechnol, Austria; Gregor Mendel Inst, Austria
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- Mairhofer, Mario (author)
- Med Univ Vienna, Austria; Univ Appl Sci Upper Austria, Austria
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- Zhu, Xiaowei (author)
- Stanford Univ, CA 94305 USA
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- Schuetz, Birgit (author)
- Med Univ Vienna, Austria
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- Hannibal, Roberta L. (author)
- Stanford Univ, CA USA; Second Genome, CA USA
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- Lindau, Robert (author)
- Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten
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- Weil, Beatrix (author)
- Med Univ Vienna, Austria
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- Ernerudh, Jan (author)
- Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Region Östergötland, Klinisk immunologi och transfusionsmedicin
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- Neesen, Juergen (author)
- Med Univ Vienna, Austria
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- Egger, Gerda (author)
- Med Univ Vienna, Austria
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- Mikula, Mario (author)
- Med Univ Vienna, Austria
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- Roehrl, Clemens (author)
- Med Univ Vienna, Austria
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- Urban, Alexander E. (author)
- Stanford Univ, CA USA
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- Baker, Julie (author)
- Stanford Univ, CA USA
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- Knoefler, Martin (author)
- Med Univ Vienna, Austria
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- Pollheimer, Juergen (author)
- Med Univ Vienna, Austria
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(creator_code:org_t)
- 2018-10-12
- 2018
- English.
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In: PLOS Genetics. - : PUBLIC LIBRARY SCIENCE. - 1553-7390 .- 1553-7404. ; 14:10
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https://journals.plo...
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https://doi.org/10.1...
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Abstract
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- 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) beta-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.
Subject headings
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Velicky, Philipp
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Meinhardt, Gudru ...
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Plessl, Kerstin
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Vondra, Sigrid
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Weiss, Tamara
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Haslinger, Peter
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show more...
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Lendl, Thomas
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Aumayr, Karin
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Mairhofer, Mario
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Zhu, Xiaowei
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Schuetz, Birgit
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Hannibal, Robert ...
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Lindau, Robert
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Weil, Beatrix
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Ernerudh, Jan
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Neesen, Juergen
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Egger, Gerda
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Mikula, Mario
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Roehrl, Clemens
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Urban, Alexander ...
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Baker, Julie
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Knoefler, Martin
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Pollheimer, Juer ...
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Cell Biology
- Articles in the publication
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PLOS Genetics
- By the university
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Linköping University