ΔNP63 defines an exocrine-committed multipotent progenitor subset in the murine pancreas
Coolens, K.; Van der Vliet, M.; Van Campenhout, J.; del Pozo, N.; Torres-Cano, A.; Olson, C.; Xu, J.; Lickert, H.; Rovira, M.; Houbracken, I.; Baldan, J.; Real, F. X.; Spagnoli, F. M.; Rooman, I.
Show abstract
Cellular plasticity underpins heterogeneity in embryogenic progenitor cells and cancer cells. The transcription factor deltaNp63 ({Delta}Np63) has been implicated in regulating cellular plasticity in several epithelial tissues. Despite a recently established role in steering plasticity of pancreatic cancer, {Delta}Np63 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 {Delta}NP63 in the embryonic pancreas. {Delta}NP63 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 {Delta}NP63 in knock-out mice leads to hypotrophic exocrine acini with reduced levels of differentiation markers. In summary, {Delta}Np63 confers heterogeneity within the MPP compartment, supporting exocrine cell development. These new insights in developmental plasticity have potential implications for pancreatic regeneration and cancer.
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