Single-Nucleus and In Situ RNA–Sequencing Reveal Cell Topographies in the Human Pancreas

Background & AimsMolecular evidence of cellular heterogeneity in the human exocrine pancreas has not been yet established because local concentration and cascade hydrolytic enzymes that can rapidly degrade cells RNA upon pancreatic resection. We sought to better understand composition neonates adults healthy diseased conditions using single-cell sequencing approaches.MethodsWe innovated single-nucleus RNA-sequencing protocols profiled more than 120,000 from pancreata adult neonatal donors. validated findings fluorescence situ hybridization, sequencing, computational approaches.ResultsWe created first comprehensive atlas including epithelial nonepithelial constituents, uncovered 3 distinct acinar cell types, with possible implications for homeostatic inflammatory processes pancreas. The comparison data showed a different endocrine tissue, highlighting tissue dynamics occurring during development. By applying spatial cartography, involving proximity mapping through we found specific type neighborhoods, dynamic topographies pancreas, principles morphologic organization organ. Furthermore, similar analyses chronic pancreatitis biopsy samples presence acinar-REG+ cells, reciprocal association between macrophages activated stellate new potential role tuft this disease.ConclusionsOur be interrogated biology provides crucial reference set comparisons map foundations diseases. Molecular approaches. disease. Our