Dysregulated lncRNAs regulate human umbilical cord mesenchymal stem cell differentiation into insulin-producing cells by forming a regulatory network with mRNAs

• HUC-MSCs can be efficiently differentiated into insulin-producing cells using small molecules, offering a promising cell source for diabetes therapy. • Transcriptome profiling reveals dynamic expression of lncRNAs and mRNAs during differentiation, with specific lncRNAs co-expressed with key pancreatic development genes (PROX1, JARID2). • Multiple signaling pathways (NF-κB, MAPK, HIPPO, PI3K-Akt, p53) are implicated in the regulation of insulin secretion by lncRNAs. • Identified lncRNAs (e.g., AC009014.3, CTBP1-AS2, XLOC_050969) serve as potential therapeutic targets and biomarkers for improving IPC differentiation and transplantation outcomes.