Ggnbp2 Is Essential for Pregnancy Success via Regulation of Mouse Trophoblast Stem Cell Proliferation and Differentiation

Biology of Reproduction
Shengqiang LiZhenmin Lei

Abstract

The Ggnbp2 null mutant embryos died in utero between Embryonic Days 13.5 to 15.5 with dysmorphic placentae, characterized by excessive nonvascular cell nests consisting of proliferative trophoblastic tissue and abundant trophoblast stem cells (TSCs) in the labyrinth. Lethality of Ggnbp2 null embryos was caused by insufficient placental perfusion as a result of remarkable decreases in both fetal and maternal blood vessels in the labyrinth. These defects were accompanied by a significant elevation of c-Met expression and phosphorylation and its downstream effector Stat3 activation. Knockdown of Ggnbp2 in wild-type TSCs in vitro provoked the proliferation but delayed the differentiation with an upregulation of c-Met expression and an enhanced phosphorylation of c-Met and Stat3. In contrast, overexpression of Ggnbp2 in wild-type TSCs exhibited completely opposite effects compared to knockdown TSCs. These results suggest that loss of GGNBP2 in the placenta aberrantly overactivates c-Met-Stat3 signaling, alters TSC proliferation and differentiation, and ultimately compromises the structure of placental vascular labyrinth. Our studies for the first time demonstrate that GGNBP2 is an essential factor for pregnancy success acting throug...Continue Reading

References

Jul 4, 2001·Nature Reviews. Genetics·J Rossant, J C Cross
Feb 2, 2002·Science·Ali H Brivanlou, James E Darnell
May 4, 2002·Molecular and Cellular Endocrinology·J C CrossS L Adamson
Sep 5, 2002·Nature Reviews. Molecular Cell Biology·David E Levy, J E Darnell
Feb 25, 2003·Placenta·J C CrossJ C P Kingdom
Dec 16, 2003·Molecular and Cellular Biology·Tristan A RodriguezSally L Dunwoodie
Nov 2, 2004·Oncogene·Roger AbounaderJohn Laterra
May 13, 2005·Physiology·Erica D Watson, James C Cross
Jun 14, 2005·Trends in Molecular Medicine·Simona CorsoSilvia Giordano
Jun 21, 2005·Developmental Biology·David G Simmons, James C Cross
Nov 25, 2005·Stem Cells and Development·Kaisa L SelesniemiThomas L Brown
Jun 20, 2007·The Journal of Biological Chemistry·Kazuo AsanomaNorio Wake
Dec 7, 2007·Laboratory Investigation; a Journal of Technical Methods and Pathology·Yunqing LiRoger Abounader
Feb 21, 2009·Biology of Reproduction·Amanda N Sferruzzi-PerriSarah A Robertson
Jul 1, 2009·Proceedings of the National Academy of Sciences of the United States of America·Anne DupressoirThierry Heidmann
Sep 17, 2009·Mechanisms of Development·Ahmed H K El-HashashSusan J Kimber
Oct 31, 2009·The International Journal of Developmental Biology·Dong Hu, James C Cross
Nov 4, 2009·Molecular and Cellular Biology·S J TunsterR M John
Dec 10, 2009·Science Signaling·Andrea BertottiLivio Trusolino
Apr 7, 2010·The Journal of Clinical Investigation·Emin MaltepeSusan J Fisher
Sep 2, 2010·Cell Stem Cell·Jian YangAustin Smith
Nov 26, 2010·Nature Reviews. Molecular Cell Biology·Livio TrusolinoPaolo M Comoglio
Nov 26, 2010·Biology of Reproduction·R Michael Roberts, Susan J Fisher
Jan 14, 2011·Journal of Gastroenterology and Hepatology·Takahiro NakamuraKunio Matsumoto
Mar 23, 2011·Oncogene·A M DulakJ M Siegfried
Jun 2, 2011·Proceedings of the National Academy of Sciences of the United States of America·Yunqing LiJohn Laterra
Jul 29, 2011·The Biochemical Journal·Hiroyuki HiraiNobuaki Kikyo
Nov 30, 2011·The Journal of Biological Chemistry·Kazuo AsanomaM A Karim Rumi
Dec 1, 2011·Therapeutic Advances in Medical Oncology·Shawna Leslie Organ, Ming-Sound Tsao
Jan 10, 2012·Reproduction : the Official Journal of the Society for the Study of Fertility·Peter L Pfeffer, David J Pearton
Sep 6, 2013·Biology of Reproduction·Jill L SeabrookQuinton A Winger
Jan 21, 2014·The International Journal of Biochemistry & Cell Biology·Rachel Barrow-McGee, Stéphanie Kermorgant
Jan 28, 2014·Current Biology : CB·Hannah T StuartJosé C R Silva

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Citations

Jul 29, 2018·Journal of Cellular and Molecular Medicine·Kaimin GuoZhenmin Lei
Jun 9, 2017·Scientific Reports·Anqi ChenBeate Brand-Saberi
Aug 22, 2017·The American Journal of Pathology·Lingyun LiuZhenmin Lei

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Methods Mentioned

BETA
gene-trap
genotyping
PCR
gene trap
Assay
transfection
electrophoresis
electrophoretic mobility shift assay

Software Mentioned

MicroSuite
TotalLab
Olympus MicroSuite

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