A transgenic mouse marking live replicating cells reveals in vivo transcriptional program of proliferation

Dev Cell. 2012 Oct 16;23(4):681-90. doi: 10.1016/j.devcel.2012.08.009. Epub 2012 Sep 20.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biomarkers / analysis
  • Biomarkers / metabolism
  • Cell Cycle
  • Cell Differentiation
  • Cell Proliferation*
  • Cell Survival
  • Cyclin B1 / genetics
  • Cyclin B1 / metabolism
  • Flow Cytometry
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Hepatocytes / cytology*
  • Hepatocytes / metabolism
  • Mice
  • Mice, Transgenic
  • NIH 3T3 Cells
  • Oligonucleotide Array Sequence Analysis
  • Real-Time Polymerase Chain Reaction
  • Transcription, Genetic / genetics*
  • Transcriptome*

Substances

  • Biomarkers
  • Cyclin B1
  • Green Fluorescent Proteins

Associated data

  • GEO/GSE39966