Fig. 2: Systematic reconstruction of the cellular trajectories of mouse embryogenesis.

a, Overview of approach. Cells from each pair of adjacent stages were projected into the same embedding space¹³. UMAP visualizations of coembedded cells from E6.25 and E6.5 are shown separately (middle column) or together (top right). A k-NN heuristic was applied to infer one or several pseudoancestors for each of the cell states observed at the later time point (bottom right). b, Histogram of all calculated edge weights. The y axis is on a log₂ scale. Edges with weights above 0.2 (red line) were retained. Top edges are those with the highest weight amongst all potential antecedents of each cell state. c, Directed acyclic graph showing inferred relationships between cell states across early mouse development. Each row corresponds to one of 94 cell-type annotations, columns to developmental stages spanning E3.5 to E13.5, nodes to cell states and node colors to germ layers. All edges with weights above 0.2 are shown in grayscale. Of note, placental tissues were not actively retained during the isolation of embryos from later time points⁴. E8.5a and E8.5b were essentially treated as two distinct time points, because they are bridging datasets that are substantially different from a technical perspective (Fig. 1a and Extended Data Fig. 2). Di, diencephalon; EmVE, embryonic visceral endoderm; ExE, extraembryonic; ExVE, extraembryonic visceral endoderm; MHB, midbrain–hindbrain boundary; PNS, peripheral nervous system.