A Single-Cell Transcriptome Atlas of the Human Pancreas

TLDR

Understanding organ function requires an inventory of cell types and marker genes, but in the human pancreas reliable markers are scarce, so transcriptome studies on pooled islets obscure rare cell types and subpopulations. We aimed to overcome this challenge by developing an automated platform to profile thousands of single pancreatic cells. The platform combines FACS, robotics, and CEL‑Seq2 to obtain transcriptomes from deceased organ donors, enabling in silico purification of all main pancreatic cell types. The atlas reveals cell type‑specific transcription factors, a REG3A‑positive acinar subpopulation, and identifies CD24 and TM4SF4 as markers for purifying live alpha and beta cells, providing a resource for deeper insight into pancreatic biology and diabetes pathophysiology.

Abstract

To understand organ function, it is important to have an inventory of its cell types and of their corresponding marker genes. This is a particularly challenging task for human tissues like the pancreas, because reliable markers are limited. Hence, transcriptome-wide studies are typically done on pooled islets of Langerhans, obscuring contributions from rare cell types and of potential subpopulations. To overcome this challenge, we developed an automated platform that uses FACS, robotics, and the CEL-Seq2 protocol to obtain the transcriptomes of thousands of single pancreatic cells from deceased organ donors, allowing in silico purification of all main pancreatic cell types. We identify cell type-specific transcription factors and a subpopulation of REG3A-positive acinar cells. We also show that CD24 and TM4SF4 expression can be used to sort live alpha and beta cells with high purity. This resource will be useful for developing a deeper understanding of pancreatic biology and pathophysiology of diabetes mellitus.