Combinatorial transcription factor activities on open chromatin induce embryonic heterogeneity in vertebrates

We applied chromatin accessibility and single cell transcriptome analyses to explore the emergence of heterogeneity and underlying gene-regulatory mechanisms during early gastrulation in Xenopus. TF activity was inferred by integrating chromatin accessibility and single cell transcriptomics. Our results show that combinatorial activity of zygotically expressed transcription factors acts on maternally-regulated accessible chromatin to induce organizer gene expression. Overall design: ATAC-seq on Xenopus embryos (stage 9, 10.5, 12 and 16) and gastrula stage embryo explants (Animal cap and Dorsal marginal zone). RNA-seq on animal caps overexpressed with Foxb1, Foxb1 + Eomes, Eomes, Irx3, Irx3 + Otx2 and Lhx8 mRNA. ScRNA-seq on Animal cap and Dorsal marginal zone explants. scATAC-seq was performed on stage 10.5 Xenopus embryos.