Comparative human embryo-mapping reveals neural bias of neuromesodermal progenitors in stem cell axial elongation models
Elongation of the human body axis is driven by the coordinated differentiation of neural and mesodermal tissues. Pluripotent stem cell-based organoid models recapitulate key aspects of axial elongation, but how they relate to the regional organization of axial development in the embryo remains unclear. Here, we map scRNA-seq from twelve stem cell-based axial organoids to a stage-matched embryo. Integrated transcriptomic and trajectory analyses show that human axial development involves three origins: forebrain neural progenitors, primitive streak mesoderm, and neuromesodermal progenitors (NMPs) with posterior potency. Axial organoids capture subsets of these origins, and contain NMPs with strong neural bias. A multivariate regression model linking pathway modulation to cell type frequencies revealed a key role of TGF-{beta} inhibition in the transition from anterior to posterior progenitors. Together, these findings clarify how the human body axis is partitioned into distinct domains by coordinated progenitor states and signaling.