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Single nucleus and in situ RNA sequencing reveals cell topographies in the human pancreas

By Luca Tosti, Yan Hang, Olivia Debnath, Sebastian Tiesmeyer, Timo Trefzer, Katja Steiger, Foo Wei Ten, Soeren Lukassen, Simone Ballke, Anja A. Kühl, Simone Spieckermann, Rita Bottino, Naveed Ishaque, Wilko Weichert, Seung K Kim, Roland Eils, Christian Conrad

Posted 14 Aug 2019
bioRxiv DOI: 10.1101/733964

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 Statement The authors have declared no competing interest.

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