Both type 1 and type 2 diabetes can be attributed to a failure of insulin-producing β-cells. For the development of regenerative therapies, the reconstitution of β-cell mass under metabolically challenging conditions has therefore attracted great research interest. The concept of interconversion of different pancreatic cell types is emerging, but its quantitative contribution to the cell-autonomous process, i.e. without any genetic or pharmacological manipulations, of β-cells turnover upon metabolic challenges remains largely unknown.
The results of Ye and colleagues suggest that adult β-cells preferentially originate from cells with relatively small developmental distance and high pre-existing abundance, and the relative contribution can be changed by metabolic insults or pharmacological interventions. The authors demonstrate the general usefulness of their lineage tracing system for the comprehensive and quantitative analysis of pancreatic cell fate and for the development of regenerative therapies.Full Text