Differentiation dynamics, postnatal fate and plasticity potential of murine embryonic pancreatic endocrine cells

Diabetes is characterized by the loss of functional insulin-producing β-cells. Thus, one axis of research now is to produce new functional β-cells either in vitro from stem cells or in situ from mature cells. For both strategies, success will depend on our knowledge on the biology of pancreatic endocrine cells. Here, we better characterize these cells from development. We use inducible cell-lineage tracing in mice to label insulin-, glucagon- and somatostatin-producing cells during specific periods of development and we study their fate in the adult islet. We observed that i) there is no postnatal neogenesis of β-, α- and δ-cells meaning that they all emerge in utero ii) α-cells emerge continuously during the entire organogenesis while δ-cells emerge in two waves and that iii) a small fraction of adult endocrine cells derive from precursors having expressed transiently a hormone gene different of the one expressed by the mature form. Finally, in diabetic conditions, we reveal heterogeneity in plasticity potential among adult α-cell population related to their timing of emergence