Esco2 restrains pathological endothelial-to-mesenchymal transition through hidden isoform regulation in a Roberts syndrome model

This study used conditional Esco2 deletion in embryonic yolk sac endothelium to investigate gene-expression, transcript-isoform, and chromatin-occupancy changes associated with endothelial dysfunction. Short-read single-cell RNA sequencing of E9.5 control and Esco2-deficient yolk sacs was used to define endothelial and endothelial-to-mesenchymal transition (EndMT)-associated cell states.

Single-cell long-read isoform sequencing (ScISOr-seq) was used to resolve transcript isoform usage and identify isoform switching not apparent from gene-level expression. In parallel, Esco2 CUT&Tag was performed on FACS-isolated GFP+ Lyve1-lineage cells from E9.5 yolk sacs to define genomic regions associated with Esco2 occupancy. Together, these datasets provide complementary gene-level, isoform-level, and chromatin-occupancy profiles for investigating Esco2-dependent regulation of endothelial state during early vascular development.