At blastocyst stage, mammalian embryos consist of the committed progenitors for the placental trophoblast, the extraembryonic endoderm (yolk sac endoderm), and the epiblast lineage (which includes all “somatic” cell types). In vitro, the trophobla...
At blastocyst stage, mammalian embryos consist of the committed progenitors for the placental trophoblast, the extraembryonic endoderm (yolk sac endoderm), and the epiblast lineage (which includes all “somatic” cell types). In vitro, the trophoblast and epiblast precursors are represented by trophoblast stem (TS) and embryonic stem (ES) cell lines, respectively, and the extraembryonic endoderm precursors are represented by extraembryonic endoderm precursor (XENP) cell lines, which our laboratory isolated first. Despite of their extraembryonic commitment, XENP cells can easily convert into many somatic cell types in vitro, i.e. they are plastic and multipotent, like their ES cell sibling.
We now discovered that cell lines that are similar to XENP cells can be easily isolated from the yolk sacs of post-gastrulation. These yolk sac-derived XENP-like (YXL) cell lines share with XENP cells the characteristic morphology, growth factor requirements, and key markers. The YXL cell lines emerge from explanted yolk sac with the same high speed as XENP cells emerge from explanted blastocyst (<1 week). And using a single nucleotide polymorphism, we found that female yolk sac-derived XENP-like cell lines exhibit non-random (paternal) X chromosome inactivation, definitively excluding a somatic origin. These data suggest that contrary to current opinion, extraembryonic endoderm precursor cells persist in the mature yolk sac, and that they can give rise to YXL cell lines. YXL cells are indistinguishable from XENP cells, and are of extraembyonic endoderm origin.
Study of YXL cells will be useful for understanding yolk sac biology and mammalian stem cell hierarchies in general. Therefore, in addition to their own therapeutic potentials, XENP cells and YXL cells are of general interest for regenerative medicine.