MYCL-mediated reprogramming expands pancreatic insulin-producing cells

Nat Metab. 2022 Feb;4(2):254-268. doi: 10.1038/s42255-022-00530-y. Epub 2022 Feb 10.


β cells have a limited capacity for regeneration, which predisposes towards diabetes. Here, we show that, of the MYC family members, Mycl plays a key role in proliferation of pancreatic endocrine cells. Genetic ablation of Mycl causes a reduction in the proliferation of pancreatic endocrine cells in neonatal mice. By contrast, the expression of Mycl in adult mice stimulates the proliferation of β and α cells, and the cells persist after withdrawal of Mycl expression. A subset of the expanded α cells give rise to insulin-producing cells after this withdrawal. Transient Mycl expression in vivo is sufficient to normalize the hyperglycaemia of diabetic mice. In vitro expression of Mycl similarly provokes active replication in islet cells, even in those from aged mice. Finally, we show that MYCL stimulates the division of human adult cadaveric islet cells. Our results demonstrate that the induction of Mycl alone expands the functional β-cell population, which may provide a regenerative strategy for β cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental*
  • Glucagon-Secreting Cells* / metabolism
  • Humans
  • Insulin / metabolism
  • Insulin-Secreting Cells* / metabolism
  • Islets of Langerhans* / metabolism
  • Mice
  • Pancreatic Hormones / metabolism


  • Insulin
  • Pancreatic Hormones