From scRNA-seq to therapeutic targets: Unveiling the impact of activated mast cells on intestinal dysfunction in acute pancreatitis

Abstract

Wei et al reported a comprehensive single-cell transcriptomic analysis of the small intestine during early acute pancreatitis (AP) and identified activated mast cells and their secretion of CCL5 as pivotal factors driving gut barrier dysfunction. By integrating scRNA-seq with in vitro and in vivo functional assays, this study advances our understanding of the cellular and molecular events underlying AP-associated intestinal injury. In this commentary, I highlight the methodological innovations employed in the study, contextualize its findings in the literature, and propose directions for future research. As an avid researcher in single-cell sequencing, I approached this letter with a spirit of academic inquiry and welcome any further discussion or corrections that may enhance my understanding.

Keywords: Acute pancreatitis; Single-cell RNA sequencing; Mast cells; CCL5; Intestinal barrier

Core Tip: Applying advanced single-cell transcriptomics, Wei et al’s study elucidates the cellular heterogeneity of the intestine during early acute pancreatitis (AP) and identifies activated mast cells and their CCL5 secretion which are key contributors to gut barrier disruption. These findings provide novel insights into AP pathophysiology and highlight potential avenues for targeted therapeutic interventions. Moreover, the study underscores the value of integrative, multidimensional approaches in deciphering complex inflammatory responses.