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

• Published in: Stem cell reports 2018-12, Vol.11 (6), p.1551-1564
• Main Authors: Krentz, Nicole A.J., Lee, Michelle Y.Y., Xu, Eric E., Sproul, Shannon L.J., Maslova, Alexandra, Sasaki, Shugo, Lynn, Francis C.
• Format: Article
• Language: English
• Subjects: Animals; Cell Differentiation; Cell Lineage; cell therapy; CyT49; diabetes; Embryo, Mammalian - cytology; endocrine progenitors; hESCs; Human Embryonic Stem Cells - metabolism; Humans; Mice; Mouse Embryonic Stem Cells - metabolism; mT/mG; Neurog3; Pancreas - cytology; pancreas development; Resource; RNA - metabolism; scRNA-seq; Single-Cell Analysis; Time Factors; Transcriptome - genetics
• ISSN: 2213-6711; 2213-6711
• DOI: 10.1016/j.stemcr.2018.11.008

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. [Display omitted] •Single-cell transcriptome of embryonic mouse pancreas and hESC-derived cells•Identification of novel cell types during mouse pancreas development•Pseudotime analysis reveals developmental trajectories of endocrine cell lineage•hESC-derived endocrine cells resemble immature β cells 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.