Elucidating Pancreatic Ductal Adenocarcinoma Carcinogenesis at Single-Cell Resolution and Identifying Subtype Specific Drug Candidates.

ABSTRACT: Although single-cell analyses have advanced our understanding of pancreatic ductal adenocarcinoma (PDAC), most studies to date have focused on primary and metastatic tumors. Here, we map cell composition, phenotypic plasticity, and microenvironmental remodeling from human normal pancreas through preneoplastic lesions to PDAC, with the preneoplastic phase recognized as a critical window for carcinogenesis. We pinpoint genes that are persistently dysregulated throughout malignant transformation and are associated with a poor prognosis. Focusing on ductal and acinar cells as the principal origins of PDAC, we delineate malignant preneoplastic cell clusters that exhibit strong carcinogenic potential. Immune profiling reveals marked expansion and functional reprogramming of macrophages during di

SUBMITTER: Chen J 

PROVIDER: S-EPMC12732769 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature