title: A transgenic mouse marking live replicating cells reveals in vivo transcriptional program of proliferation.
abstract: Most adult mammalian tissues are quiescent, with rare cell divisions serving to maintain homeostasis. At present, the isolation and study of replicating cells from their in vivo niche typically involves immunostaining for intracellular markers of proliferation, causing the loss of sensitive biological material. We describe a transgenic mouse strain, expressing a CyclinB1-GFP fusion reporter, that marks replicating cells in the S/G2/M phases of the cell cycle. Using flow cytometry, we isolate live replicating cells from the liver and compare their transcriptome to that of quiescent cells to reveal gene expression programs associated with cell proliferation in vivo. We find that replicating hepatocytes have reduced expression of genes characteristic of liver differentiation. This reporter system provides a powerful platform for gene expression and metabolic and functional studies of replicating cells in their in vivo niche.
authors.affiliation: Department of Cell and Developmental Biology, The Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
authors.forename: Agnes
authors.initials: A
authors.lastname: Klochendler
authors.forename: Noa
authors.initials: N
authors.lastname: Weinberg-Corem
authors.forename: Maya
authors.initials: M
authors.lastname: Moran
authors.forename: Avital
authors.initials: A
authors.lastname: Swisa
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pochet
authors.forename: Virginia
authors.initials: V
authors.lastname: Savova
authors.forename: Jonas
authors.initials: J
authors.lastname: Vikeså
authors.forename: Yves
authors.initials: Y
authors.lastname: Van de Peer
authors.forename: Michael
authors.initials: M
authors.lastname: Brandeis
authors.forename: Aviv
authors.initials: A
authors.lastname: Regev
authors.forename: Finn Cilius
authors.initials: FC
authors.lastname: Nielsen
authors.forename: Yuval
authors.initials: Y
authors.lastname: Dor
authors.forename: Amir
authors.initials: A
authors.lastname: Eden
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D056744:Cyclin B1 / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D041681:NIH 3T3 Cells; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000235:genetics*; D059467:Transcriptome
chemical_list: D015415:Biomarkers; D056744:Cyclin B1; D049452:Green Fluorescent Proteins