Deciphering Pancreatic Islet β Cell and α Cell Maturation Pathways and Characteristic Features at the Single-Cell Level

Pancreatic beta and alpha cells play essential roles in maintaining glucose homeostasis. However, the mechanisms by which these distinct cell populations are generated, expand, and mature during pancreas development remain unclear. In this study, we addressed this critical question by performing a single- cell transcriptomic analysis of mouse beta and a cells sorted from fetal to adult stages. We discovered that beta and alpha cells use different regulatory strategies for their maturation and that cell proliferation peaks at different developmental times. However, the quiescent and proliferative cells in both the beta lineage and alpha lineage are synchronous in their maturation states. The heterogeneity of juvenile beta cells reflects distinct cell-cycling phases, origins, and maturation states, whereas adult beta cells are relatively homogeneous at the transcriptomic level. These analyses provide not only a high-resolution roadmap for islet lineage development but also insights into the mechanisms of cellular heterogeneity, cell number expansion, and maturation of both beta and alpha cells.