Advances in 2D and 3D imaging techniques and technologies have enabled deeper interrogation of rare pancreas bioresources, highlighting significant gaps in our knowledge, with implications for the understanding of normal development and pancreatic disease. 3D volumetric imaging of the adult pancreas has revealed that 40–50% of the total endocrine objects within the organ consist of single beta cells or small clusters of beta cells. Despite their large numbers, these constitute a relatively small proportion of the total endocrine area, and they are not routinely assessed in histological, functional, transcriptional or proteomic studies. Virtually nothing is known about their role and function across the life course.
We have now replicated the initial 3D observations by employing 2D image analysis of >250 healthy and type 1 diabetes donor pancreata across different ages using AI–assisted pipelines that have enabled the study of >450,000 endocrine objects (EOs) (Murrall et al, 2025 Science Advances). Our results reveal a dramatic change in EO architecture and number in early development. With increasing donor age, EOs occupy an ever–decreasing proportion of the total endocrine area but still remain present in high numbers into adulthood in subjects without diabetes. We carefully mapped the architectural changes within the pancreas that occur during the first few years of life and found that alterations in endocrine object size and architecture coincide with a dramatic expansion of the pancreas over the early years of life. As age increases, a marked decline in the proportional endocrine area (%) and endocrine object density occurs. This proposal will focus on expanding the donor numbers in this critical developmental window. We will employ a combination of spatial transcriptomics and multiplex immunofluorescence mapping to characterise the alterations in small endocrine object parameters, including proliferation and proximity to ductal structures, during early life.
