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Embryonic development and stem cell differentiation, during which coordinated cell fate specification takes place in a spatial and temporal context, serve as a paradigm for studying the orderly assembly of gene regulatory networks (GRNs) and the fundamental mechanism of GRNs in driving lineage determination. However, knowledge of reliable GRN annotation for dynamic development regulation, particularly for unveiling the complex temporal and spatial architecture of tissue stem cells, remains inadequate. With the advent of single-cell RNA sequencing technology, elucidating GRNs in development and stem cell processes poses both new challenges and unprecedented opportunities. This review takes a snapshot of some of this work and its implication in the regulative nature of early mammalian development and specification of the distinct cell types during embryogenesis.