腺泡细胞
急性胰腺炎
平衡
胰腺炎
胰腺
免疫系统
蓝绿藻
PDX1型
转录组
导管细胞
细胞
细胞生物学
癌症研究
医学
生物
内科学
免疫学
内分泌学
转录因子
生物化学
基因
基因表达
胆囊收缩素
受体
作者
Katherine J. Aney,Woo-Jeong Jeong,Andrés F. Vallejo,Cassandra Burdziak,Ethan Chen,Austin Wang,Pal Koak,Kellie Wise,Kirk B. Jensen,Dana Pe’er,Stephanie K. Dougan,Luciano G. Martelotto,Sahar Nissim
标识
DOI:10.1053/j.gastro.2024.01.043
摘要
Acinar cells produce digestive enzymes that impede transcriptomic characterization of the exocrine pancreas. Thus, single-cell RNA-sequencing studies of the pancreas underrepresent acinar cells relative to histological expectations, and a robust approach to capture pancreatic cell responses in disease states is needed. We sought to innovate a method that overcomes these challenges to accelerate study of the pancreas in health and disease.We introduce FixNCut, a single-cell RNA-sequencing approach in which tissue is reversibly fixed with dithiobis(succinimidyl propionate) before dissociation and single-cell preparation. We apply FixNCut to an established mouse model of acute pancreatitis, validate findings using GeoMx whole transcriptome atlas profiling, and integrate our data with prior studies to benchmark our method in both mouse and human pancreas datasets.FixNCut achieves unprecedented definition of challenging pancreatic cells, including acinar and immune populations in homeostasis and acute pancreatitis, and identifies changes in all major cell types during injury and recovery. We define the acinar transcriptome during homeostasis and acinar-to-ductal metaplasia and establish a unique gene set to measure deviation from normal acinar identity. We characterize pancreatic immune cells, and analysis of T-cell subsets reveals a polarization of the homeostatic pancreas toward type-2 immunity. We report immune responses during acute pancreatitis and recovery, including early neutrophil infiltration, expansion of dendritic cell subsets, and a substantial shift in the transcriptome of macrophages due to both resident macrophage activation and monocyte infiltration.FixNCut preserves pancreatic transcriptomes to uncover novel cell states during homeostasis and following pancreatitis, establishing a broadly applicable approach and reference atlas for study of pancreas biology and disease.
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