Cross-Species Study Reveals Pig-Human Pancreas Development Parallels

Groundbreaking Cross-Species Pancreas Development Research

Scientists have conducted a comprehensive multimodal comparison of pancreas development across mice, pigs, and humans, revealing significant evolutionary conservation between porcine and human developmental processes. According to reports published in Nature Communications, the study utilized temporally resolved single-cell multi-omics to track pancreatic organogenesis, morphogenesis, and differentiation across species.

Groundbreaking Cross-Species Pancreas Development Research
Developmental Timeline Comparisons Reveal Striking Patterns
Single-Cell Atlas Uncovers Cellular Diversity
Conserved Regulatory Networks Between Species
Endocrine Fate Allocation Differences Discovered
Implications for Diabetes Research and Developmental Biology

The research team, sources indicate, focused particularly on the pig model’s potential for identifying both species-specific and evolutionally conserved mechanisms. Their findings demonstrate that pig pancreas development shows closer resemblance to human development than to mice, especially during critical transitional phases of endocrine cell formation.

Developmental Timeline Comparisons Reveal Striking Patterns

Analysis of developmental milestones revealed significant differences in timing across species, according to the report. The formation of initial pancreatic buds occupied approximately 17% of gestation in pigs compared to 10% in humans and 12% in mice. However, later stages of pancreatic morphogenesis and islet formation progressed much faster in mice (42% of gestation) compared to the extended duration in both humans (82%) and pigs (65%).

Researchers noted that the extended development period in pigs and humans coincides with prolonged acinar terminal differentiation and islet remodeling. The report states that this temporal alignment suggests pigs may serve as a more accurate model for human pancreatic development than previously recognized.

Single-Cell Atlas Uncovers Cellular Diversity

To capture dynamic transcriptional changes, the team performed single-cell RNA sequencing on 124,869 cells isolated from pig pancreata across all three trimesters of development. Analysis identified eight distinct epithelial cell clusters, including ductal, acinar, endocrine progenitor, and multiple hormone-producing cell types.

The research revealed two particularly interesting cell populations: a transient multipotent progenitor cell cluster existing during early development (E23-40) and a persistent primed endocrine cell cluster that emerged alongside sparse NEUROG3 endocrine progenitors. Sources indicate that the latter population expressed genes coding for cytoskeletal components and cell cycle regulators throughout subsequent developmental stages.

Conserved Regulatory Networks Between Species

When comparing transcriptional features across all three species, analysts suggest that pig and human pancreatic cell types showed stronger correlation (r = 0.6-0.7) than mouse-human comparisons (r = 0.45-0.54) for certain cell populations. The study particularly noted differences in multipotent progenitor, beta, and endocrine progenitor clusters between mice and humans.

Further investigation into cis-regulatory elements revealed conserved chromatin accessibility patterns between pigs and humans for key developmental regulators. According to the analysis, both species shared active transcription factor motifs directing endocrine and exocrine lineage specification, including known regulators of endocrinogenesis such as NEUROG3, RFX3, RFX6, and NEUROD1.

Endocrine Fate Allocation Differences Discovered

The research uncovered significant differences in how endocrine progenitor cells commit to specific fates across species. Cell fate mapping revealed that in both pigs and humans, progenitors with high NEUROG3 expression already showed segregation toward either alpha or beta cell lineages. In contrast, mouse endocrine precursors maintained multipotency longer, with lineage separation occurring later in development.

Analysis of lineage driver genes showed that pigs and humans shared more overlapping genetic drivers for both alpha and beta cell fate determination compared to the set shared between mice and humans. The report states this finding further supports the closer evolutionary relationship between porcine and human pancreatic development.

Implications for Diabetes Research and Developmental Biology

The identification of conserved regulatory networks and developmental trajectories between pigs and humans has significant implications for both basic research and therapeutic development. According to analysts, the pig model may provide more relevant insights for understanding human pancreatic disorders, including diabetes, due to the closer conservation of developmental mechanisms.

Researchers noted that the study also identified diabetes risk-related genes expressed in cell-type specific patterns across species. The comprehensive comparison, sources indicate, provides a valuable resource for understanding both conserved and species-specific aspects of pancreas development that could inform future regenerative medicine approaches.