ΔNP63 defines an exocrine-committed multipotent progenitor subset in the murine pancreas

Cellular plasticity underpins heterogeneity in embryogenic progenitor cells and cancer cells. The transcription factor deltaNp63 ( ΔNp63 ) has been implicated in regulating cellular plasticity in several epithelial tissues. Despite a recently established role in steering plasticity of pancreatic cancer, ΔNp63 remains unstudied in pancreatic development. Using murine single-cell sequencing data and RNA and protein in situ stainings, we assessed the spatio-temporal expression of Trp63 and ΔNP63 in the embryonic pancreas. ΔNP63 demonstrates a transient and spatially restricted expression in the multipotent pancreatic progenitor (MPP) compartment delineating pro-exocrine progenitor cells. Lineage tracing of TP63 + cells marks a subset of MPPs and descendant exocrine acinar and centro-acinar/terminal duct cells. Lack of ΔNP63 in knock-out mice leads to hypotrophic exocrine acini with reduced levels of differentiation markers. In summary, ΔNp63 confers heterogeneity within the MPP compartment, supporting exocrine cell development. These new insights in developmental plasticity have potential implications for pancreatic regeneration and cancer.