Analysis of individual cells identifies cell-to-cell variability following induction of cellular senescence

Christopher D. Wiley, James M. Flynn, Christapher Morrissey, Ronald Lebofsky, Joe Shuga, Xiao Dong, Marc A. Unger, Jan Vijg, Simon Melov, Judith Campisi

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Senescent cells play important roles in both physiological and pathological processes, including cancer and aging. In all cases, however, senescent cells comprise only a small fraction of tissues. Senescent phenotypes have been studied largely in relatively homogeneous populations of cultured cells. In vivo, senescent cells are generally identified by a small number of markers, but whether and how these markers vary among individual cells is unknown. We therefore utilized a combination of single-cell isolation and a nanofluidic PCR platform to determine the contributions of individual cells to the overall gene expression profile of senescent human fibroblast populations. Individual senescent cells were surprisingly heterogeneous in their gene expression signatures. This cell-to-cell variability resulted in a loss of correlation among the expression of several senescence-associated genes. Many genes encoding senescence-associated secretory phenotype (SASP) factors, a major contributor to the effects of senescent cells in vivo, showed marked variability with a subset of highly induced genes accounting for the increases observed at the population level. Inflammatory genes in clustered genomic loci showed a greater correlation with senescence compared to nonclustered loci, suggesting that these genes are coregulated by genomic location. Together, these data offer new insights into how genes are regulated in senescent cells and suggest that single markers are inadequate to identify senescent cells in vivo.

Original languageEnglish (US)
JournalAging Cell
DOIs
StateAccepted/In press - 2017

Fingerprint

Cell Aging
Genes
Transcriptome
Physiological Phenomena
Population
Phenotype
Cell Separation
Pathologic Processes
Cultured Cells
Fibroblasts
Polymerase Chain Reaction

Keywords

  • Aging
  • Cellular senescence
  • Cytokines
  • Single cell
  • Transcriptomics

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Cite this

Wiley, C. D., Flynn, J. M., Morrissey, C., Lebofsky, R., Shuga, J., Dong, X., ... Campisi, J. (Accepted/In press). Analysis of individual cells identifies cell-to-cell variability following induction of cellular senescence. Aging Cell. https://doi.org/10.1111/acel.12632

Analysis of individual cells identifies cell-to-cell variability following induction of cellular senescence. / Wiley, Christopher D.; Flynn, James M.; Morrissey, Christapher; Lebofsky, Ronald; Shuga, Joe; Dong, Xiao; Unger, Marc A.; Vijg, Jan; Melov, Simon; Campisi, Judith.

In: Aging Cell, 2017.

Research output: Contribution to journalArticle

Wiley, Christopher D. ; Flynn, James M. ; Morrissey, Christapher ; Lebofsky, Ronald ; Shuga, Joe ; Dong, Xiao ; Unger, Marc A. ; Vijg, Jan ; Melov, Simon ; Campisi, Judith. / Analysis of individual cells identifies cell-to-cell variability following induction of cellular senescence. In: Aging Cell. 2017.
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