Integrated multi-omic atlas reveals the hierarchy of spatiotemporal regulatory networks of mouse gastrulation

Spatiotemporal coordination of cellular and molecular events is crucial for cell fate commitment during mouse gastrulation. However, the high-precision mechanisms governing the timing and spatial dynamics remain poorly understood. Here, we present a time-series single-cell multi-omic dataset of the gastrulating mouse embryos and construct a hierarchical gene regulatory landscape. Integrating this with real three-dimensional transcriptomic coordinate, we created ST-MAGIC and ST-MAGIC (+) atlas, dissecting the spatiotemporal logics of regulatory networks and signaling responsiveness underpinning the lineage commitment at gastrulation. Specifically, we delineated the multi-omic basis for left-right symmetry breaking events in the gastrula and also revealed the spatiotemporal molecular relay for axial mesendoderm lineage, where early and intermediate transcription factors first open the chromatin regions and setup the responsiveness to signaling, followed by terminal factors to consolidate the transcriptomic architecture. In summary, our study presents a spatiotemporal regulatory logic framework of mouse gastrulation for advancing our understanding of mammalian embryogenesis. Spatiotemporal coordination of cellular and molecular events is crucial for cell fate commitment. Here, Yang et al. describe how transcription factors, signaling pathways, and epigenomic states regulate left-right patterning and axial mesendoderm lineage commitment during mouse gastrulation.