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

• Verfasst von: Tosti, Luca [VerfasserIn]
• Verfasst von: Hang, Yan [VerfasserIn]
• Verfasst von: Debnath, Olivia [VerfasserIn]
• Verfasst von: Tiesmeyer, Sebastian [VerfasserIn]
• Verfasst von: Trefzer, Timo [VerfasserIn]
• Verfasst von: Steiger, Katja [VerfasserIn]
• Verfasst von: Ten, Foo Wei [VerfasserIn]
• Verfasst von: Lukassen, Sören [VerfasserIn]
• Verfasst von: Ballke, Simone [VerfasserIn]
• Verfasst von: Kühl, Anja A. [VerfasserIn]
• Verfasst von: Spieckermann, Simone [VerfasserIn]
• Verfasst von: Bottino, Rita [VerfasserIn]
• Verfasst von: Ishaque, Naveed [VerfasserIn]
• Verfasst von: Weichert, Wilko [VerfasserIn]
• Verfasst von: Kim, Seung K. [VerfasserIn]
• Verfasst von: Eils, Roland [VerfasserIn]
• Verfasst von: Conrad, Christian [VerfasserIn]
• Titel: Single-nucleus and in situ RNA-sequencing reveal cell topographies in the human pancreas
• Verf.angabe: Luca Tosti, Yan Hang, Olivia Debnath, Sebastian Tiesmeyer, Timo Trefzer, Katja Steiger, Foo Wei Ten, Sören Lukassen, Simone Ballke, Anja A. Kühl, Simone Spieckermann, Rita Bottino, Naveed Ishaque, Wilko Weichert, Seung K. Kim, Roland Eils, and Christian Conrad
• Jahr: 2021
• Umfang: 26 S.
• Fussnoten: Available online 16 November 2020 ; Gesehen am 10.05.2021
• Titel Quelle: Enthalten in: Gastroenterology
• Ort Quelle: New York, NY : Elsevier, 1949
• Jahr Quelle: 2021
• Band/Heft Quelle: 160(2021), 4, Seite 1330-1344.e11
• ISSN Quelle: 1528-0012
• DOI: doi:10.1053/j.gastro.2020.11.010
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Acinar Heterogeneity
• Sach-SW: Chronic Pancreatitis
• Sach-SW: Healthy Pancreas
• Sach-SW: Postnatal Development
• K10plus-PPN: 1757541578

Abstract

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