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Endodermal origin of yolk-sac-derived teratomas
H Sobis1, A Verstuyf, M Vandeputte
1Rega Institute for Medical Research, University of Leuven, Belgium.
Abstract:
Mutant mice deficient in glucose-6-phosphate dehydrogenase were used to induce teratomas. This enzyme is linked to the X chromosome, which can be inactivated in female embryo. The differences in the enzyme activity between yolk sac mesoderm and embryo versus yolk sac endoderm can be detected in female concepti by using appropriate crosses of wild-type and G6PD-deficient mice. Histochemical study showed that the dual cell population was observed in heterozygous embryos and in the embryomas derived from them. The teratomas derived from the corresponding yolk sac, however, were G6PD-positive from wild-type and G6PD-negative from homozygous enzyme-deficient mothers. We conclude that yolk-sac-derived teratomas are of endodermal origin because of the fact that the paternal X chromosome is inactivated in the yolk sac endoderm, whereas in the yolk sac mesoderm, as in the embryo, the inactivation is at random.
Insights
Teratomas derived from mouse yolk sacs originate from endodermal cells. This is because the paternal X chromosome is inactivated in yolk sac endoderm, unlike in mesoderm or embryos where inactivation is random.
Area of Science:
- Developmental Biology
- Genetics
- Teratoma Research
Background:
- Glucose-6-phosphate dehydrogenase (G6PD) is an X-linked enzyme crucial for cellular metabolism.
- X chromosome inactivation in female mammals leads to mosaicism for X-linked gene expression.
- Teratomas are tumors with diverse cell types, often arising from pluripotent cells.
Purpose of the Study:
- To investigate the cellular origin of yolk sac-derived teratomas using G6PD deficiency as a marker.
- To determine the pattern of X chromosome inactivation in different embryonic and extraembryonic tissues.
- To elucidate the developmental lineage of teratomas formed from the yolk sac.
Main Methods:
- Utilized mutant mice deficient in glucose-6-phosphate dehydrogenase (G6PD).
- Employed crosses between wild-type and G6PD-deficient mice to generate heterozygous and homozygous concepti.
- Performed histochemical analysis to detect G6PD enzyme activity in embryonic and teratoma tissues.
Main Results:
- Heterozygous embryos and their derived embryomas exhibited dual G6PD activity, indicating random X inactivation.
- Teratomas derived from the yolk sac showed distinct G6PD activity patterns based on maternal genotype.
- Yolk sac-derived teratomas from homozygous deficient mothers were G6PD-negative, while those from wild-type mothers were G6PD-positive.
Conclusions:
- Yolk sac-derived teratomas originate from endodermal cells.
- This conclusion is supported by the non-random paternal X chromosome inactivation observed specifically in yolk sac endoderm.
- Contrasts with random X inactivation in yolk sac mesoderm and the embryo proper.