title: Single cell transcriptomic profiling of mouse pancreatic progenitors.
abstract: The heterogeneity of the developing pancreatic epithelium and low abundance of endocrine progenitors limit the information derived from traditional expression studies. To identify genes that characterize early developmental tissues composed of multiple progenitor lineages, we applied single-cell RNA-Seq to embryonic day (e)13.5 mouse pancreata and performed integrative analysis with single cell data from mature pancreas. We identified subpopulations expressing macrophage or endothelial markers and new pancreatic progenitor markers. We also identified potential α-cell precursors expressing glucagon (Gcg) among the e13.5 pancreatic cells. Despite their highGcgexpression levels, these cells shared greater transcriptomic similarity with other e13.5 cells than with adult α-cells, indicating their immaturity. Comparative analysis identified the sodium-dependent neutral amino acid transporter,Slc38a5, as a characteristic gene expressed in α-cell precursors but not mature cells. By immunofluorescence analysis, we observed SLC38A5 expression in pancreatic progenitors, including in a subset of NEUROG3+ endocrine progenitors and MAFB+ cells and in all GCG+ cells. Expression declined in α-cells during late gestation and was absent in the adult islet. Our results suggest SLC38A5 as an early marker of α-cell lineage commitment.
authors.affiliation: Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.|Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Diana E
authors.identifier: 0000-0002-2410-8951
authors.initials: DE
authors.lastname: Stanescu
authors.affiliation: Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.|Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; and.
authors.forename: Reynold
authors.initials: R
authors.lastname: Yu
authors.affiliation: Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.|Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; and.
authors.forename: Kyoung-Jae
authors.initials: KJ
authors.lastname: Won
authors.affiliation: Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; stoffers@mail.med.upenn.edu.|Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Doris A
authors.initials: DA
authors.lastname: Stoffers
mesh_terms: D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D016000:Cluster Analysis; D004622:Embryo, Mammalian / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics; D020869:Gene Expression Profiling; D007515:Islets of Langerhans / Q000166:cytology; D051379:Mice; D008954:Models, Biological; D010179:Pancreas / Q000166:cytology*; D059010:Single-Cell Analysis; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D026921:Amino Acid Transport Systems, Neutral; C588123:SNAT5 protein, mouse
keywords: alpha cell marker; pancreas development; single cell RNA-Seq