Fig. 3: Bifurcation point identification during the AEC-to-HE transition.

a Developmental trajectory starts from early AEC (eAEC) and bifurcates toward late AEC (lAEC) or HEC. b Left: Close-up of mouse trajectory concerning AEC-Pre-HE-EC/HE transition from Fig. 2a. Right: Expression levels of marker genes for mouse cell types-Nr2f2 (venous marker), Pecam1 (CD31-coding gene) and Cdh5 (endothelial markers), Ltbp4 (mature arterial marker), Ptprc (CD45-coding gene, hematopoietic marker). c Query projection of mouse scRNA-seq data from (Hou et al.¹⁶) into mouse ensemble (gray). eAEC (blue), early AEC; lAEC (red), late AEC; HEC (orange). d Module scores for mouse and human cell types/sub-clusters based on gene sets from GO terms and TF module 1. e Query projection of human GJA5⁺ AEC from Crosse et al.²⁷ into human ensemble (gray). f Human developmental trajectory starting from C4 and branching at C6 toward GJA5⁺ AEC and C7. g Top five biological pathways enriched by DEGs between mouse pre-HE and HE, and analogous terms enriched by DEGs between pre-HE and EC. Red/blue GO terms indicate enrichment by up/down-regulated DEGs. h Top 5 biological pathways enriched by DEGs between human C6 and C7, and matching terms enriched by DEGs between C6 and GJA5⁺ AEC. Red/blue GO terms signify enrichment by up/downregulated DEGs. i, j Local regulatory networks among the top ten upstream regulators of upregulated DEGs between mouse pre-HE and HE (i), and between human C6 and C7 (j). Network edges represent co-regulatory relationships with edges involving MYC, highlighted in red.