{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T19:17:23Z","timestamp":1789586243602,"version":"build-2803163510"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acute pancreatitis (AP) ranges from mild to severe, and severe disease frequently causes multi-organ damage, with intestinal injury being a major complication. The mechanisms underlying SAP-induced intestinal injury remain unclear, particularly regarding spatial cellular reorganization and functional interactions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study constructed a severe acute pancreatitis (SAP) rat model and employed single-nucleus RNA sequencing (snRNA-seq) and spatial transcriptome sequencing (stRNA-seq) technologies to systematically analyze the dynamic changes in intestinal cellular composition, spatial distribution, and function during SAP-induced intestinal injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      snRNA-seq identified 18 major ileal cell populations spanning epithelial, immune, stem\/TA, and stromal compartments. SAP was associated with compositional remodeling characterized by downward trends in Lgr5\n                      <jats:sup>+<\/jats:sup>\n                      \/Olfm4\n                      <jats:sup>+<\/jats:sup>\n                      stem cells, TA1, goblet cells, and Paneth cells, with a reciprocal increase in enterocytes, although most proportion changes did not reach statistical significance at the animal level. Spatial transcriptomics independently captured SAP-associated tissue remodeling, including a significant reduction in Paneth cells accompanied by increases in fat cells, macrophages, goblet cells, and TA2 cells. Across epithelial lineages, SAP induced a transcriptional shift toward immune interaction with up-regulation of antigen presentation\u2013related genes (e.g., Cd74) and down-regulation of antimicrobial\/barrier effectors (e.g., Defa24, Pla2g2a, Dmbt1), which was corroborated by spatial expression patterns and spatially variable gene programs enriched for host defense responses. Pseudotime analysis suggested a redistribution of epithelial states along the stem\/TA-to-enterocyte continuum, with relative depletion of early states and expansion of enterocyte-dominant states in SAP. CellChat analysis revealed globally intensified intercellular communication and nominated FN1 as the pathway with the highest differential information flow, with Lgr5\n                      <jats:sup>+<\/jats:sup>\n                      stem cells predicted as prominent FN1 senders targeting enterocytes and smooth muscle cells. SCENIC identified reduced activity and expression of Hmga2\/Myb regulons in stem compartments, and immunofluorescence showed decreasing trends in Hmga2\/Myb-positive Olfm4\n                      <jats:sup>+<\/jats:sup>\n                      and Lgr5\n                      <jats:sup>+<\/jats:sup>\n                      stem cells in SAP.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Integrated single-nucleus and spatial transcriptomics reveal that SAP is accompanied by spatially organized ileal remodeling, epithelial immune-interacting rewiring, and altered neighborhood architecture, together with an ECM-centered FN1 signaling axis and attenuated Hmga2\/Myb-associated regulatory programs in stem compartments. These findings provide a spatially informed cellular framework and generate testable hypotheses for mechanisms underlying impaired epithelial regeneration during SAP-associated intestinal injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1719902","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T06:43:25Z","timestamp":1769755405000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Single-nucleus and spatial transcriptomics reveal intestinal cellular heterogeneity, differentiation, and cell communication mechanisms in SAP-induced intestinal 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