Single-cell pseudotime and cell communication analysis of pancreatic cancer.

[BACKGROUND] Pancreatic cancer (PC) is among the most aggressive and lethal malignancies, characterized by development within a complex tumor microenvironment (TME) that includes a desmoplastic stroma composed of extracellular matrix (ECM) and various cellular components.

[OBJECTIVES] This study aims to elucidate the cellular and molecular mechanisms regulating PC progression through an integrated analysis of single-cell pseudotime trajectories and intercellular communication.

[MATERIAL AND METHODS] We constructed pseudotime trajectories using single-cell RNA sequencing (scRNA-seq) data from PC tissues to trace the developmental progression of cancer cells. Transitional cell states and critical genes involved in the shift from early-to-advanced disease stages were identified. Through a comprehensive analysis, we pinpointed key transcription factors and signaling pathways implicated in tumor progression. Expression of stemness-associated genes in pancreatic stellate cells (PSC) was validated using immunofluorescence and transmission electron microscopy (TEM). Additionally, cell-cell communication analysis was performed to examine interactions within the TME, with particular emphasis on ligand-receptor pairings.

[RESULTS] Our analysis identified key transcription factors and signaling pathways that drive the cellular transitions associated with cancer progression. The findings revealed extensive intercellular crosstalk between cancer cells, stromal fibroblasts, and diverse immune cell subpopulations. Notably, the study underscored the distinct functional contributions of these cell populations to tumor development, immune evasion and metastatic dissemination.

[CONCLUSIONS] The study uncovers the complex cellular diversity and intercellular crosstalk in PC, providing novel avenues for therapeutic interventions and early predictive markers in diagnosis. These findings support the potential for more targeted, personalized treatment strategies in combating PC.