Single cell transcriptome profiling of mouse and hESC-derived pancreatic progenitors

Abstract

Human embryonic stem cells (hESCs) are a potential unlimited source of insulin-producing {beta}-cells for diabetes treatment. A greater understanding of how {beta}-cells form during embryonic development will improve current hESC differentiation protocols. As {beta}-cells are formed from NEUROG3-expressing endocrine progenitors, this study focused on characterizing the single-cell transcriptomes of mouse and hESC-derived endocrine progenitors. To do this, 7,223 E15.5 and 6,852 E18.5 single cells were isolated from Neurog3-Cre; Rosa26mT/mG embryos, allowing for enrichment of endocrine progenitors (yellow; tdTomato + EGFP) and endocrine cells (green; EGFP). From a NEUROG3-2A-eGFP CyT49 hESC reporter line (N5-5), 4,497 hESC-derived endocrine progenitor cells were sequenced. Differential expression analysis reveals enrichment of markers that are consistent with progenitor, endocrine, or novel 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 {beta}-like cells from hESCs.