MiR-302 regulates pancreatic progenitor pool and pancreatic size [mRNA-seq]

Disruptions in pancreatic development lead to health issues such as pancreatic agenesis and congenital diabetes mellitus. Understanding pancreatic organogenesis is critical for identifying disease mechanisms and developing regenerative therapies. The pancreas consists of endocrine and exocrine cells, both of which are derived from multipotent progenitor cells (MPCs). MPC proliferation and differentiation are tightly controlled by multiple mechanisms, including post-transcriptional regulation by miRNAs. However, these regulatory factors are not fully understood. Here, we profiled miRNA expression in MPCs and identified that miR-302 was highly enriched during the earliest stages of pancreatic development. Loss of miR-302 resulted in reduced pancreatic size without altering the proportions of endocrine and exocrine cells at E17.5, suggesting that miR-302 regulates MPC number rather than differentiation. Transcriptomic analysis at E10.5 revealed that miR-302 modulates genes involved in the Wnt signaling pathway and cell cycle progression. Notably, miR-302 prolonged S phase in MPCs, leading to slower cell proliferation and a smaller MPC pool at E10.5. These findings provide the first comprehensive miRNA profile during early pancreatic development and establish miR-302 as a critical regulator of MPC number and pancreas size.