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

Nicole A. J. Krentz(University of British Columbia), Michelle Y. Y. Lee(BC Children's Hospital), Eric E. Xu(University of British Columbia), Shannon L. J. Sproul(University of British Columbia), Alexandra Maslova(University of British Columbia), Shugo Sasaki(University of British Columbia), Francis C. Lynn(University of British Columbia)
Stem Cell Reports
December 1, 2018
10.1016/j.stemcr.2018.11.008
Cited by 126Open Access
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Abstract

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.

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