Trophoblast stem cells rescue placental defect in SOCS3-deficient mice.
Stem cells have important clinical and experimental potentials. Trophoblast stem (TS) cells possess the ability to differentiate into trophoblast subtypes in vitro and contribute to the trophoblast lineage in vivo. Suppressor of cytokine signaling 3 (SOCS3) is a negative regulator of cytokine signaling. Targeted disruption of SOCS3 revealed embryonic lethality on E12.5; it was caused by placental defect with enhanced leukemia inhibitory factor receptor signaling. A complementation of the wild-type (WT) placenta by using tetraploid rescue technique showed that the embryonic lethality in SOCS3-deficient embryo was due to the placental defect. Here we demonstrate that TS cells supplementation rescues placental defect in SOCS3-deficient embryos. In the rescued placenta, TS cells were integrated into the placental structure, and a substantial structural improvement was observed in the labyrinthine layer that was disrupted in the SOCS3-deficient placenta. Importantly, by supplying TS cells, living SOCS3-deficient embryos were detected at term. These results indicate a functional contribution of TS cells in the placenta and their potential application.
Takahashi
Yutaka
Y
Howard Hughes Medical Institute, Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. takahash@med.kobe-u.ac.jp
Dominici
Massimo
M
Swift
John
J
Nagy
Cristie
C
Ihle
James N
JN
D000818:Animals; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010920:Placenta / Q000002:abnormalities / Q000196:embryology*; D010922:Placenta Diseases / Q000473:pathology / Q000517:prevention & control; D011247:Pregnancy; D033581:Stem Cell Transplantation; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000502:physiology*; D014327:Trophoblasts / Q000637:transplantation*
C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins