Abstract
The derivation of stable multipotent trophoblast stem (TS) cell lines from preimplantation, and early postimplantation mouse embryos has been reported previously. FGF4, and its receptor FGFR2, have been identified as embryonic signaling factors responsible for the maintenance of the undifferentiated state of multipotent TS cells. Here we report the derivation of stable TS-like cell lines from the vole M. rossiaemeridionalis, in the absence of FGF4 and heparin. Vole TS-like cells are similar to murine TS cells with respect to their morphology, transcription factor gene expression and differentiation in vitro into derivatives of the trophectoderm lineage, and with respect to their ability to invade and erode host tissues, forming haemorrhagic tumours after subcutaneous injection into nude mice. Moreover, vole TS-like cells carry an inactive paternal X chromosome, indicating that they have undergone imprinted X inactivation, which is characteristic of the trophoblast lineage. Our results indicate that an alternative signaling pathway may be responsible for the establishment and stable proliferation of vole TS-like cells.
Highlights
The trophectoderm is the first specialised cell lineage formed by the developing embryo in mammals
Vole stem cells belong to the trophectoderm lineage We derived stable trophoblast stem (TS)-like cell lines from vole M. rossiaemeridionalis blastocysts
We detected the presence of the transcription factors Cdx2 and Eomes, which are critical for the determination and maintenance of the murine trophectoderm lineage [47,48], in the derived vole cell lines
Summary
The trophectoderm is the first specialised cell lineage formed by the developing embryo in mammals. It surrounds the blastocoel and undifferentiated inner cell mass (ICM) that will give rise to the embryo proper and to the extraembryonic endoderm tissues. Multipotent cells of the trophectoderm undergo differentiation into specialised cell types that form the developing placenta. Mural trophectoderm surrounding the blastocoel forms primary giant cells that invade the uterus and lead to embryo implantation. The ICM-contacting polar trophectoderm continues to proliferate and forms the extraembryonic ectoderm (ExE) and, later, the ectoplacental cone [1], which serves as one of the sources of the chorionic plate, and of secondary giant cells (Fig. 1) [2]. Cells in close proximity to the ICM/epiblast remain diploid and retain the ability to proliferate and give rise to trophoblast stem (TS) cells when cultured in vitro [4]
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