MAPC culture condition supports the derivation of cells with nascent hypoblast features from bone marrow and blastocysts

Rat Extraembryonic Endoderm Precursor (XEN-P) cells resemble the nascent hypoblast of the blastocyst. Here we show that rat Multipotent Adult Progenitor Cell (rMAPC) lines derived from bone marrow (BM) exhibit salient nascent hypoblast characteristics. We could not identify cells with hypoblast features in rat BM, but they appeared after prolonged in vitro culture under rMAPC conditions. However, rMAPC culture conditions supported the very rapid isolation of new lines with nascent hypoblast features from rat blastocysts that were more homogenous than XEN-P cells isolated on feeders. The gene expression profile, growth factor requirement, Oct4 promoter methylation, and in vitro/vivo differentiation potential of cells isolated using rMAPC culture conditions from BM or blastocysts or XEN-P cells were highly similar. We conclude that the three cell populations have characteristics of hypoblast stem cells (HypoSC) and that rMAPC culture conditions support the isolation of XEN-P/HypoSC from the blastocyst and induction of HypoSC from BM.