初期ヒト多能性幹細胞からアクセス可能な細胞運命の広範なスペクトル

Naïve human pluripotent stem cells (hPSCs) represent an in vitro analog of the pre-implantation epiblast - the founder tissue of the embryo proper. A widely held assumption, based on prior studies in the mouse system, was that naïve hPSCs are restricted in their differentiation potential toward more mature stages of epiblast development, as a prelude to gastrulation. However, over the past 5 years, a growing body of literature has demonstrated that naïve hPSCs have an expanded lineage potential toward a broad range of embryonic and extraembryonic fates and can even be used as a starting point for generating 8-cell-like cells. The most emphatic demonstration of the broad lineage potential of naïve hPSCs is their remarkable capacity to self-organize into blastocyst-like structures ("blastoids") that model all three lineages of the pre-implantation embryo and can be cultured to post-implantation stages. Here, we discuss the broad spectrum of cell fates accessible from naïve hPSCs and the signaling pathways that guide the exit from the ground state of human pluripotency.