Molecular and genetic regulation of pig pancreatic islet cell development

Seokho Kim, Robert L. Whitener, Heshan Peiris, Xueying Gu, Charles A. Chang, Jonathan Y. Lam, Joan Camunas-Soler, Insung Park, Romina J. Bevacqua, Krissie Tellez, Stephen R. Quake, Jonathan R. T. Lakey, Rita Bottino, Pablo J. Ross, Seung K. Kim

Aug 08, 2019

Received Date: 17th July 19

Reliance on rodents for understanding pancreatic genetics, developmental biology and islet function could limit progress in developing interventions for human diseases like diabetes mellitus. Similarities of pancreas morphology and function, and pancreatic disease modeling in pigs suggest that porcine and human pancreas developmental biology may have useful homologies. However, little is known about pig pancreas development. To fill this knowledge gap, we investigated fetal and neonatal pig pancreas at multiple, crucial developmental stages using modern experimental approaches. Purification of islet beta-, alpha- and delta-cells via flow cytometry followed by high-throughput transcriptome analysis (RNA-Seq) provided comprehensive gene expression profiles. Morphometric analysis revealed dynamic developmental endocrine cell allocation and islet architectural similarities between pig and human islets. Gene expression analysis identified cell- and stage-specific expression in sorted pig beta- and alpha-cells, and revealed that pig and human beta-cells and alpha-cells shared characteristic molecular and developmental features not observed in mouse beta-cells or alpha-cells. Over 150 causal or candidate ‘diabetes risk’ genes identified by human studies had dynamic developmental expression in pig beta- and alpha-cells. Our analysis also unveiled scores of signaling pathways linked to native islet beta-cell functional maturation. Thus, the findings, conceptual advances, and resources detailed here show how pig pancreatic islet studies complement or surpass other systems for understanding the developmental programs that generate functional beta- and alpha-cells, and that are relevant to human diseases like diabetes mellitus.

Read in full at bioRxiv.

This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

Nature Communications

Nature Research, Springer Nature