miR-302 regulates pancreatic progenitor pool and pancreatic size

Disruptions in pancreatic development can lead to health issues such as pancreatic agenesis and congenital diabetes mellitus. Understanding pancreatic organogenesis is critical for elucidating 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 the number of MPCs rather than their differentiation. Transcriptomic analysis at E10.5 revealed that mir-302 modulates genes associated with the Wnt signaling pathway and cell cycle progression. Notably, loss of mir-302 prolonged the S phase in MPCs, resulting in 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.