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©The Author(s) 2025.
World J Gastroenterol. Jul 7, 2025; 31(25): 107865
Published online Jul 7, 2025. doi: 10.3748/wjg.v31.i25.107865
Published online Jul 7, 2025. doi: 10.3748/wjg.v31.i25.107865
Table 1 Key outcome summary
Key outcome | Observation in AP small intestine | Implication |
Intestinal cellular heterogeneity | scRNA-seq of the small intestine identified 17 distinct cell clusters from > 33000 cells across the control, AP1, and AP2 samples | Provides a high-resolution atlas of the small-intestinal cell composition and reveals dynamic shifts during early AP |
Intestinal MC activation | scRNA-seq showed an apparent reduction of MC recovery but immunofluorescence staining (c-Kit and toluidine blue) confirmed stable MC counts with degranulation | Highlights activation-induced MC fragility during dissociation and underscores MC mediator release as a driver of barrier dysfunction |
CCL5 upregulation in intestinal MCs | scRNA-seq and flow cytometry demonstrated significant CCL5 overexpression in MCs in the AP1 and AP2 groups | Identifies CCL5 as a key chemokine, mediating neutrophil and macrophage recruitment to the gut barrier |
Tight junction disruption in small intestine | IHC revealed decreased expression of ZO-1 and occludin in AP1 and AP2 intestinal epithelia | Confirms compromised epithelial barrier integrity at early stages of AP |
Programmed cell death in enterocytes | IHC showed increase in cleaved caspase-3 (apoptosis) and p-MLKL (necroptosis) levels in intestinal enterocytes from the control to AP1 to AP2 group | Demonstrates enterocyte loss via multiple cell-death pathways contributing to barrier breakdown |
Table 2 Recommendations for future research
Recommendation | Specific approach (key points) |
Longitudinal single-cell profiling | (1) Time points (post AP induction): Early (2 hours, 6 hours, and 24 hours), mid (3 days and 7 days) and late (14 days and 28 days); and (2) Assays: FITC-dextran permeability and serum LPS (barrier); histological score and IHC/FACS for neutrophil/macrophage infiltration along with IL-6/TGF-β (inflammation); Masson’s staining and Col1a1/Col3a1 mRNA (fibrosis); and 16S rRNA sequencing (microbiome recovery) |
MC activation mechanisms | (1) Techniques: scATAC-seq + phospho-proteomics on sorted MCs; and (2) Targets: PAR2/tryptase, the FcεRI-independent pathway, and NF-κB/AP-1 |
Human spatial validation | (1) Samples: Ileal/jejunal biopsies (Ranson < 3 vs ≥ 3); (2) Platform: 10 × Visium or GeoMX DSP; and (3) Readouts: MC density, CCL5, and immune infiltrates |
Preclinical intervention studies | (1) Drugs: Cromolyn sodium and Maraviroc; and (2) Endpoints: Gut histology, 16S rRNA, cytokines, and 72 hours survival |
- Citation: Li B. From scRNA-seq to therapeutic targets: Unveiling the impact of activated mast cells on intestinal dysfunction in acute pancreatitis. World J Gastroenterol 2025; 31(25): 107865
- URL: https://www.wjgnet.com/1007-9327/full/v31/i25/107865.htm
- DOI: https://dx.doi.org/10.3748/wjg.v31.i25.107865