Skp2 contributes to cell cycle progression in trophoblast stem cells and to placental development
| Autor: | Masaaki Nishiyama, Yuhei Yamauchi, Hideyuki Shimizu, Akihiro Nita, Yoshiharu Muto, Hirokazu Nakatsumi, Keiichi I. Nakayama |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Placenta
Mutant Biology Mice 03 medical and health sciences Pregnancy Genetics SKP2 medicine Animals Cyclin-Dependent Kinase Inhibitor p57 S-Phase Kinase-Associated Proteins Cell Proliferation 030304 developmental biology Mice Knockout 0303 health sciences Kinase Stem Cells Cell Cycle Trophoblast Cell Differentiation Embryo Cell Biology Cell cycle Embryo Mammalian Placentation Rats Trophoblasts Cell biology Mice Inbred C57BL medicine.anatomical_structure Female Stem cell Cyclin-Dependent Kinase Inhibitor p27 |
| Zdroj: | Genes to Cells. 25:427-438 |
| ISSN: | 1365-2443 1356-9597 |
| DOI: | 10.1111/gtc.12769 |
| Popis: | All trophoblast subtypes of the placenta are derived from trophoblast stem cells (TSCs). TSCs have the capacity to self-renew, but how the proliferation of these cells is regulated in the undifferentiated state has been largely unclear. We now show that the F-box protein Skp2 regulates the proliferation of TSCs and thereby plays a pivotal role in placental development in mice on the C57BL/6 background. The placenta of Skp2-/- mouse embryos on the C57BL/6 background was smaller than that of their Skp2+/+ littermates, with the mutant embryos also manifesting intrauterine growth retardation. Although the Skp2-/- mice were born alive, most of them died before postnatal day 21, presumably as a result of placental defects. Depletion of Skp2 in TSCs cultured in the undifferentiated state resulted in a reduced rate of proliferation and arrest of the cell cycle in G1 phase, indicative of a defect in self-renewal capacity. The cell cycle arrest apparent in Skp2-deficient TSCs was reversed by additional ablation of the cyclin-dependent kinase inhibitor (CKI) p57 but not by that of the CKI p27. Our results thus suggest that Skp2-mediated degradation of p57 is an important determinant of the self-renewal capacity of TSCs during placental development, at least in mice of certain genetic backgrounds. |
| Databáze: | OpenAIRE |
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