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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.

Original publication

DOI

10.1016/j.stemcr.2018.11.008

Type

Journal article

Journal

Stem Cell Reports

Publication Date

11/12/2018

Volume

11

Pages

1551 - 1564

Keywords

CyT49, Neurog3, cell therapy, diabetes, endocrine progenitors, hESCs, mT/mG, pancreas development, scRNA-seq, Animals, Cell Differentiation, Cell Lineage, Embryo, Mammalian, Human Embryonic Stem Cells, Humans, Mice, Mouse Embryonic Stem Cells, Pancreas, RNA, Single-Cell Analysis, Time Factors, Transcriptome