biostudies-literatureWen DNICHD NIH HHSFoundation for the National Institutes of HealthNational Institutes of HealthNIGMS NIH HHSNIH HHS102342https://www.ebi.ac.uk/biostudies/studies/S-EPMC12279028biostudies-literatureUnknown92The term 'totipotency' has often been misapplied in stem cell research to describe cells with embryonic and extraembryonic bipotentiality, despite a lack of evidence that they can generate an entire organism from a single cell. Additionally, no specific term currently distinguishes bipotential stem cells from pluripotent cells, which contribute poorly to extraembryonic tissues. This review examines the developmental continuum from totipotency to pluripotency in early embryos and revisits the previously proposed concept of plenipotency in preimplantation development. We evaluate emerging stem cell models that exhibit bipotentiality but have lost the ability to autonomously initiate and sustain the sequential fate decisions necessary to develop into a complete organism. Unlike totipotent embCurrent opinion in genetics & developmentTotipotency or plenipotency: rethinking stem cell bipotentiality.PMC12279028R01HD097268R01 GM129380R01GM129380R01 HD0972681R21OD031973R21 OD031973R01 HD095938R01 GM129157Wen DWang JfalseTotipotency or plenipotency: rethinking stem cell bipotentiality.The term 'totipotency' has often been misapplied in stem cell research to describe cells with embryonic and extraembryonic bipotentiality, despite a lack of evidence that they can generate an entire organism from a single cell. Additionally, no specific term currently distinguishes bipotential stem cells from pluripotent cells, which contribute poorly to extraembryonic tissues. This review examines the developmental continuum from totipotency to pluripotency in early embryos and revisits the previously proposed concept of plenipotency in preimplantation development. We evaluate emerging stem cell models that exhibit bipotentiality but have lost the ability to autonomously initiate and sustain the sequential fate decisions necessary to develop into a complete organism. Unlike totipotent emb2025-01-01T00:00:00Z2025 Jun2026-03-16T07:07:17.879Z2025-08-17T03:05:45.1ZS-EPMC122790284010711610.1016/j.gde.2025.102342