RT Journal Article SR Electronic T1 Single-Cell Protein Atlas of Transcription Factors Reveals the Combinatorial Code for Spatiotemporal Patterning the C. elegans Embryo JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.06.30.178640 DO 10.1101/2020.06.30.178640 A1 Xuehua Ma A1 Zhiguang Zhao A1 Long Xiao A1 Weina Xu A1 Yangyang Wang A1 Yanping Zhang A1 Gang Wu A1 Zhuo Du YR 2020 UL http://biorxiv.org/content/early/2020/07/07/2020.06.30.178640.abstract AB A high-resolution protein atlas is essential for understanding the molecular basis of biological processes. Using protein-fusion reporters and imaging-based single-cell analyses, we present a protein expression atlas of C. elegans embryogenesis encompassing 266 transcription factors (TFs) in nearly all (90%) lineage-resolved cells. Single-cell analysis reveals a combinatorial code and cascade that elucidate the regulatory hierarchy between a large number of lineage-, tissue-, and time-specific TFs in spatiotemporal fate patterning. Guided by expression, we identify essential functions of CEH-43/DLX, a lineage-specific TF, and ELT-1/GATA3, a well-known skin fate specifier, in neuronal specification; and M03D4.4 as a pan-muscle TF in converging muscle differentiation in the body wall and pharynx. Finally, systems-level analysis of TF regulatory state uncovers lineage- and time-specific kinetics of fate progression and widespread detours of the trajectories of cell differentiation. Collectively, our work reveals a single-cell molecular atlas and general principles underlying the spatiotemporal patterning of a metazoan embryo.Competing Interest StatementThe authors have declared no competing interest.