Single-cell RNA sequencing reveals PANoptosis signatures of acinar cells, macrophages, and neutrophils during injury and repair in acute pancreatitis.

Authors

Weizhi Zhang, Feng Cao

Published in

Frontiers in cell and developmental biology. Volume 14. Pages 1948502. Epub Sep 28, 2026.

Abstract

Acute pancreatitis (AP) involves acinar cell injury, inflammation, and tissue remodeling. Although regulated cell death pathways contribute to AP progression, the cell type-specific features and dynamics of PANoptosis remain unclear. This study aimed to characterize PANoptosis-associated signatures in pancreatic cell populations at single-cell resolution.
A caerulein plus lipopolysaccharide-induced mouse AP model was established. Pancreatic tissues from wild-type, AP, and early recovery groups were analyzed by single-cell RNA sequencing. Major cell types and subclusters were identified using marker genes. PANoptosis-related programs were evaluated using multiple scoring algorithms, pseudotime analysis, and functional enrichment. Histological and immunohistochemical analyses were performed for validation.
Single-cell profiling revealed extensive remodeling of the pancreatic cellular microenvironment during AP and recovery, characterized by acinar cell loss and increased macrophage and neutrophil infiltration. Acinar cell subclustering identified 12 transcriptionally distinct subpopulations, including injury-associated subsets with ductal-like features marked by Krt19, Epcam, Lcn2, and Krt7. Trajectory analysis suggested dynamic transitions from mature digestive enzyme-producing acinar states toward stress-associated and inflammatory states. PANoptosis-related signatures were most prominent in inflammatory acinar subsets, particularly Cluster 10, followed by Clusters 7, 4, and 5. Macrophage and neutrophil analyses further identified PANoptosis-high inflammatory subsets, especially macrophage Cluster 4 and neutrophil Cluster 4.
This study establishes a single-cell atlas of AP injury and recovery, revealing cell-specific PANoptosis programs in acinar cells and inflammatory populations, highlighting PANoptosis as a potential link between acinar injury, immune activation, and pancreatic remodeling.

PMID:
42865768
Bibliographic data and abstract were imported from PubMed on 13 Oct 2026.

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