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Series GSE235874 Query DataSets for GSE235874
Status Public on Feb 28, 2024
Title A Novel Approach for Pancreas Transcriptomics Reveals the Cellular Landscape in Homeostasis and Acute Pancreatitis
Organism Mus musculus
Experiment type Other
Summary BACKGROUND & AIMS: Acinar cells produce digestive enzymes that impede transcriptomic characterization of the exocrine pancreas. Thus, single-cell RNA-sequencing (scRNA-seq) 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. METHODS: We introduce FixNCut, a scRNA-seq approach where tissue is reversibly fixed with dithiobis(succinimidyl propionate) prior to dissociation and single-cell preparation. We apply FixNCut to an established mouse model of acute pancreatitis, validate findings using GeoMx whole transcriptome atlas (WTA) profiling, and integrate our data with prior studies to benchmark our method in both mouse and human pancreas datasets. RESULTS: 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 towards 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. CONCLUSIONS: 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.
Overall design Pancreatitis was induced in C57BL/6 mice at 8-9 weeks of age using intraperitoneal caerulein injections on two consecutive days once every hour for 8 hours. Formalin-fixed paraffin-embedded microarray tissue sections (5 ┬Ám) were used for Nanostring's GeoMX Whole Transcriptome Atlas Digital Spatial Profiling.
Contributor(s) Aney KJ, Jeong W, Chen EE, Jensen K, Wise K, Martelotto L, Nissim S
Citation(s) 38325760
Submission date Jun 26, 2023
Last update date May 29, 2024
Contact name Sahar Nissim
Organization name Brigham and Women's Hospital
Department Genetics
Lab Nissim
Street address 77 Avenue Louis Pasteur
City Boston
State/province MA
ZIP/Postal code 02115
Country USA
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (57)
GSM7511062 Pancreas, control, rep1
GSM7511063 Pancreas, control, rep2
GSM7511064 Pancreas, control, rep3
BioProject PRJNA987747

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Supplementary file Size Download File type/resource
GSE235874_BioProbeInformation.xlsx 1.0 Mb (ftp)(http) XLSX
GSE235874_QC_BQC_Q3Norm_matrixonly.xlsx 7.0 Mb (ftp)(http) XLSX
GSE235874_QC_BQC_raw_matrixonly.xlsx 3.4 Mb (ftp)(http) XLSX
GSE235874_RAW.tar 4.1 Mb (http)(custom) TAR (of DCC)
GSE235874_TargetProperties_raw.xlsx 830.0 Kb (ftp)(http) XLSX
GSE235874_segmentSummary_readTypes.xlsx 20.9 Kb (ftp)(http) XLSX
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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