Journal: Nature Communications

Article Title: A multimodal cross-species comparison of pancreas development

doi: 10.1038/s41467-025-64774-4

Figure Lengend Snippet: a –c For each species: circular projection of CellRank-calculated fate probabilities for each cell toward the terminal states (outer labels); and UMAPs detailing endocrine progenitors branching, with the integrated pancreas atlas showing NEUROG3 expression (red) and endocrine progenitor cluster boundaries (black), and an insert showing endocrine progenitor subclusters with overlaid CellRank-inferred trajectories (arrows). d Line plots showing the cumulative number of CellRank-derived beta-cell (top) and alpha-cell (bottom) lineage drivers in mouse and pig that overlap with human orthologs, plotted across correlation score thresholds (Supplementary Data ). Solid lines show significant driver numbers (Benjamini-Hochberg FDR-corrected p-value < 0.05). Shaded regions indicate the number of genes obtained when using the lower and upper bounds of the 95% confidence interval for the corresponding correlation score. e, f Heatmaps displaying modeled gene expression patterns for human beta-cell ( e ) and alpha-cell ( f ) lineage driver gene clusters (identified by hierarchical clustering) across pig, human, and mouse along pseudotemporal trajectories (left to right: 0 → 1). Annotations indicate species-conserved pathways and representative genes for each cluster. (corr., correlation; n, number of conserved genes that are expressed in > 20% of endocrine progenitor subclusters) g –i Comparison of NEUROG3 TF targets identified in human/pig pancreas and hESC model (conserved targets in blue). g, h Circular GRN graphs showing first- and second-order NEUROG3 targets from human scGLUE-jointed scRNA/ATAC-seq data ( g ) and pig multiomic data ( h ). Nodes represent TFs. Edge color indicates regulatory interaction types (orange, activating; gray, inhibiting); i NEUROG3 TF targets in hESC model with inducible NEUROG3 expression. ChIP-seq-identified direct targets are shaded. Differentially expressed TFs comparing cells with/without NEUROG3 expression are indicated by arrows (red, upregulated; blue, downregulated). a – f scRNA-seq of pancreatic cells from wild-type and INS -eGFP pigs. h Multiome analysis of pancreatic cells from PTF1A -codon-improved-Cre/ROSA-mTmG pigs. Detailed sample information is provided in Supplementary Data .

Article Snippet: The parent human embryonic stem cell (hESC) line WA01 (H1) was obtained from WiCell.

Techniques: Expressing, Derivative Assay, Gene Expression, Comparison, ChIP-sequencing