Study of Mecom in the development of the pancreas

Mecom is a transcription factor of which we discovered that it allows adult pancreatic acinar cells to dedifferentiate under stress conditions, thereby avoiding cell death. This study aimed at determining the expression and role of this transcription factor during the embryonic development of the mouse pancreas. A transgenic mouse model harboring Mecom (Evi-1) with exon 4 (which is present in all Evi-1 isoforms) flanked by LoxP sites, was crossed with Pdx1-Cre mice. In the resulting Pdx1-Cre Mecomf/f mice, Mecom is knocked-out in all cells that expressed Pdx1. The embryonic samples were analyzed using immunohistochemical stainings, RNA in situ hybridization (RNAScope) and RT-qPCR. We observed that Mecom is highly expressed in many developing organs, including stomach, kidney and lungs. In the pancreas, relatively high levels were present at E13.5 and E16.5, both in ECad+ epithelial and Vim+ mesenchymal compartments. This confirms public single cell RNAseq datasets from mouse and human embryos. These observations suggest that MECOM has a transient role in pancreatic embryonic development. In Mecomf/f mice, Mecom expression in epithelial nuclei was significantly reduced by 74.05 ± 5.66% (p<0.01). However, when assessing progenitor and acinar dedifferentiation markers (Cpa1, Sox9, Pdx1) and proliferation marker Ki67 and Ctnnb1, no expression changes were observed between the two genotypes. Interestingly, the adult Mecomf/f mice showed a trend of lowered glycemia and pancreas weight, hinting towards a potential link with endocrine development. In conclusion, MECOM is transiently expressed in the embryonic mouse pancreas, while there is no apparent phenotype in exocrine cell differentiation and proliferation.