Loss-of-function of ALDH3B2 transdifferentiates human pancreatic duct cells into beta-like cells

Beta cell regeneration is achieved predominantly by self-replication, especially in rodents, but it was also shown that pancreatic duct cells can transdifferentiate into beta cells. How pancreatic duct cells are transdifferentiated and whether we can manipulate transdifferentiation to replenish beta cell mass is not well understood.

Using a genome-wide Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) screen, we found that loss-of-function of Aldehyde dehydrogenase family 3 member B2 (ALDH3B2) was sufficient to transdifferentiate human pancreatic duct cells into functional beta-like cells. The transdifferentiated cells had substantially increased expression of beta cell marker genes, secreted insulin in response to glucose, and lowered blood glucose to near normal when transplanted into streptozotocin (STZ)-induced diabetic mice for 6 weeks.