Single-Cell Transcriptome Profiling of Mouse and hESC-Derived Pancreatic Progenitors

Abstract

Summary: Human embryonic stem cells (hESCs) are a potential unlimited source of insulin-producing β cells for diabetes treatment. A greater understanding of how β cells form during embryonic development will improve current hESC differentiation protocols. All pancreatic endocrine cells, including β cells, are derived from Neurog3-expressing endocrine progenitors. This study characterizes the single-cell transcriptomes of 6,905 mouse embryonic day (E) 15.5 and 6,626 E18.5 pancreatic cells isolated from Neurog3-Cre; Rosa26mT/mG embryos, allowing for enrichment of endocrine progenitors (yellow; tdTomato + EGFP) and endocrine cells (green; EGFP). Using a NEUROG3-2A-eGFP CyT49 hESC reporter line (N5-5), 4,462 hESC-derived GFP+ cells were sequenced. Differential expression analysis revealed enrichment of markers that are consistent with progenitor, endocrine, or previously undescribed cell-state populations. This study characterizes the single-cell transcriptomes of mouse and hESC-derived endocrine progenitors and serves as a resource (https://lynnlab.shinyapps.io/embryonic_pancreas) for improving the formation of functional β-like cells from hESCs. : In this article, Krentz and colleagues characterize the single-cell transcriptome of E15.5 and E18.5 mouse pancreatic cells and hESC-derived endocrine cells. They identify pancreatic cell-type-specific genes in the mouse and compare hESC-derived endocrine cells to fetal mouse endocrine cells and human islets. Keywords: pancreas development, scRNA-seq, endocrine progenitors, Neurog3, hESCs, mT/mG, CyT49, diabetes, cell therapy