Mapping Master Regulators of Regeneration Rhythms
Diabetes is a group of energy metabolism diseases defined by chronic hyperglycemia triggered by the inability of the body to produce and/or use sufficient insulin. Insulin is almost exclusively produced by the pancreatic β-cells. Consequently, β-cell decay triggers hyperglycaemia and diabetes. The two most prevalent forms of diabetes are ultimately characterised by significant β-cell loss. According to the extent of this deficit the murine pancreas can deploy two distinct regenerative responses: partial, however substantial, loss will trigger compensatory proliferation of the surviving β-cells, while total loss will prompt the age-specific transdifferentiation of the neighboring endocrine pancreatic islet populations. Although these mechanisms can naturally rescue the mice from diabetes, both are slow and inefficient. Thus, any future exploitation in clinics requires boosting their performance. However, to date it remains largely unknown what are the exact global regulators and networks deploying the two different cellular responses (proliferation versus transdifferentiation). By combining complex transgenic systems and omics analyses we identified a common molecular network shared between the two regenerative mechanisms and pinpointed a potential novel regulator governing this regenerative switch.