Mapping histological and functional maturation of human endocrine pancreas across early postnatal periods.

Human endocrine cell differentiation and islet morphogenesis play critical roles in determining islet cell mass and function, but the events and timeline of these processes are incompletely defined. To better understand early human islet cell development and maturation, we collected 115 pediatric pancreata and mapped morphological and spatiotemporal changes from birth through the first ten years of life. Using quantitative analyses and a combination of complementary tissue imaging approaches, including confocal microscopy and whole-slide imaging, we developed an integrated model for endocrine cell formation and islet architecture, including endocrine cell type heterogeneity and abundance, endocrine cell proliferation, and islet vascularization and innervation.

Macrophage subtypes inhibit breast cancer proliferation in culture.

Macrophages are a highly plastic cell type that adopt distinct subtypes and functional states depending on environmental cues. These functional states can vary widely, with distinct macrophages capable of displaying opposing functions. We sought to understand how macrophage subtypes that exist on two ends of a spectrum influence the function of other cells.

Interruption of glucagon signaling augments islet non-alpha cell proliferation in SLC7A2- and mTOR-dependent manners.

Objective: Dysregulated glucagon secretion and inadequate functional beta cell mass are hallmark features of diabetes. While glucagon receptor (GCGR) antagonism ameliorates hyperglycemia and elicits beta cell regeneration in pre-clinical models of diabetes, it also promotes alpha and delta cell hyperplasia. We sought to investigate the mechanism by which loss of glucagon action impacts pancreatic islet non-alpha cells, and the relevance of these observations in a human islet context.

Interruption of glucagon signaling augments islet non-alpha cell proliferation in SLC7A2- and mTOR-dependent manners.

Objective: Dysregulated glucagon secretion and inadequate functional beta cell mass are hallmark features of diabetes. While glucagon receptor (GCGR) antagonism ameliorates hyperglycemia and elicits beta cell regeneration in pre-clinical models of diabetes, it also promotes alpha and delta cell hyperplasia. We sought to investigate the mechanism by which loss of glucagon action impacts pancreatic islet non-alpha cells, and the relevance of these observations in a human islet context.