TY - JOUR T1 - Single nucleus and <em>in situ</em> RNA sequencing reveals cell topographies in the human pancreas JF - bioRxiv DO - 10.1101/733964 SP - 733964 AU - Luca Tosti AU - Yan Hang AU - Olivia Debnath AU - Sebastian Tiesmeyer AU - Timo Trefzer AU - Katja Steiger AU - Foo Wei Ten AU - Sören Lukassen AU - Simone Ballke AU - Anja A. Kühl AU - Simone Spieckermann AU - Rita Bottino AU - Naveed Ishaque AU - Wilko Weichert AU - Seung K. Kim AU - Roland Eils AU - Christian Conrad Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/05/03/733964.abstract N2 - Molecular evidence of cellular heterogeneity in the human exocrine pancreas has not been established, due to the local concentration of hydrolytic enzymes that can rapidly degrade cells and RNA upon resection. Here we innovated single-nucleus RNA sequencing protocols, and profiled more than 120,000 cells from adult and neonatal human donors to create the first comprehensive atlas of human pancreas cells, including epithelial and non-epithelial constituents. Adult and neonatal pancreata shared common features, including the presence of previously undetected acinar subtypes, but also showed marked differences in the composition of the endocrine, endothelial, and immune compartments. Spatial cartography, including cell proximity mapping through in situ sequencing, revealed dynamic developmental cell topographies in the endocrine and exocrine pancreas. Our human pancreas cell atlas can be interrogated to understand pancreatic cell biology, and provides a crucial reference set for future comparisons with diseased tissue samples to map the cellular foundations of pancreatic diseases.Competing Interest StatementThe authors have declared no competing interest. ER -