Isolation of primitive mouse extraembryonic endoderm (pXEN) stem cell lines

Mouse blastocysts contain the committed precursors of the extraembryonic endoderm (ExEn), which express the key transcription factor Oct4, depend on LIF/LIF-like factor-driven Jak/Stat signaling, and initially exhibit lineage plasticity. Previously described rat blastocyst-derived ExEn precursor-like cell lines (XENP cells/HypoSCs) also show these features, but equivalent mouse blastocyst-derived cell lines are lacking. We now present mouse blastocyst-derived cell lines, named primitive XEN (pXEN) cells, which share these and additional characteristics with the XENP cells/HypoSCs, but not with previously known mouse blastocyst-derived XEN cell lines. Otherwise, pXEN cells are highly similar to XEN cells by morphology, lineage-intrinsic differentiation potential, and multi-gene expression profile, although the pXEN cell profile correlates better with the blastocyst stage. Finally, we show that pXEN cells easily convert into XEN-like cells but not vice versa. The findings indicate that (i) pXEN cells are more representative than XEN cells of the blastocyst stage; (ii) mouse pXEN, rather than XEN, cells are homologs of rat XENP cells/HypoSCs, which we propose to call rat pXEN cells. Keywords: Stem cells, Blastocyst, Mice, Rats, Extraembryonic endoder