title: The Genetic Program of Pancreatic β-Cell Replication In Vivo.
abstract: The molecular program underlying infrequent replication of pancreatic β-cells remains largely inaccessible. Using transgenic mice expressing green fluorescent protein in cycling cells, we sorted live, replicating β-cells and determined their transcriptome. Replicating β-cells upregulate hundreds of proliferation-related genes, along with many novel putative cell cycle components. Strikingly, genes involved in β-cell functions, namely, glucose sensing and insulin secretion, were repressed. Further studies using single-molecule RNA in situ hybridization revealed that in fact, replicating β-cells double the amount of RNA for most genes, but this upregulation excludes genes involved in β-cell function. These data suggest that the quiescence-proliferation transition involves global amplification of gene expression, except for a subset of tissue-specific genes, which are "left behind" and whose relative mRNA amount decreases. Our work provides a unique resource for the study of replicating β-cells in vivo.
authors.affiliation: Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Agnes
authors.initials: A
authors.lastname: Klochendler
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Inbal
authors.initials: I
authors.lastname: Caspi
authors.affiliation: Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Noa
authors.initials: N
authors.lastname: Corem
authors.affiliation: Department of Cell and Developmental Biology, Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Maya
authors.initials: M
authors.lastname: Moran
authors.affiliation: Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Oriel
authors.initials: O
authors.lastname: Friedlich
authors.affiliation: Info-CORE, Bioinformatics Unit of the I-CORE Computation Center, and Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Sharona
authors.initials: S
authors.lastname: Elgavish
authors.affiliation: Info-CORE, Bioinformatics Unit of the I-CORE Computation Center, and Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Nevo
authors.affiliation: Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Aharon
authors.initials: A
authors.lastname: Helman
authors.affiliation: Endocrinology and Metabolism Service, Department of Internal Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Glaser
authors.affiliation: Department of Cell and Developmental Biology, Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Amir
authors.initials: A
authors.lastname: Eden
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Shalev
authors.initials: S
authors.lastname: Itzkovitz
authors.affiliation: Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel yuvald@ekmd.huji.ac.il.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Dor
mesh_terms: D000818:Animals; D002455:Cell Division / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D059467:Transcriptome