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This article discusses the implications of the recent discovery that rat bone marrow‐derived multipotent adult progenitor cells (rMAPCs), a cell type with broad somatic differentiation potential but of uncertain lineage identity, are similar to rat blastocyst‐derived extraembryonic endoderm precursor (rXENP) cells, which appear to represent the committed extraembryonic endoderm precursor of the blastocyst. It was found that under rMAPC culture conditions, rXENP cells can be homogeneously cultured and similar cells, named rat hypoblast stem cells (rHypoSCs), can be derived from rat blastocysts more rapidly and directly. The detailed comparison of rHypoSCs, rXENP cells, and rMAPCs revealed highly similar gene expression profiles and developmental potentials. The significance of these findings for embryology, stem cell biology, and medicine is discussed. Specifically, the results assign a lineage identity to rMAPCs, indicate that rMAPCs originated by environmental reprogramming, and imply that HypoSCs, XENP cells, and MAPCs possess lineage plasticity. The MAPC‐HypoSC relation also strengthens the consistency of rat and mouse embryology and consequently the idea that HypoSCs represent the committed extraembryonic endoderm precursor of the blastocyst. On this basis, it is argued that the direct comparison of HypoSCs (now available in pure form) with embryonic stem cells will be highly useful for the understanding of pluripotency and plasticity. Finally, the new findings suggest an explanation for an obscure observation on stem cell‐induced transplantation tolerance. Thus, the HypoSC/XENP/MAPC phenotype provides a unique but broadly instructive model with which to study stem cell plasticity, reprogramming, and transplantation tolerance, all central themes in regenerative medicine. S TEM  C ELLS  2013;31:620–626

Concise Review: Bone Marrow Meets Blastocyst: Lessons from an Unlikely Encounter