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

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 inmore » senescent cells and suggest that single markers are inadequate to identify senescent cells in vivo.« less

Authors:

Wiley, Christopher D. ^[1]; Flynn, James M. ^[1]; Morrissey, Christapher ^[1]; Lebofsky, Ronald ^[2]; Shuga, Joe ^[2]; Dong, Xiao ^[3]; Unger, Marc A. ^[2]; Vijg, Jan ^[3]; Melov, Simon ^[1]; Campisi, Judith ^[4]

---

+ Show Author Affiliations

1. Buck Inst. for Research on Aging, Novato, CA (United States)
2. Fluidigm Corporation, South San Francisco, CA (United States)
3. Albert Einstein College of Medicine, Bronx, NY (United States). Dept. of Genetics
4. Buck Inst. for Research on Aging, Novato, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Publication Date:

Tue Jul 11 00:00:00 EDT 2017

Research Org.:

Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Org.:

USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

OSTI Identifier:

1625859

Grant/Contract Number:  

AC02-05CH11231

Resource Type:

Accepted Manuscript

Journal Name:

Aging Cell

Additional Journal Information:

Journal Volume: 16; Journal Issue: 5; Journal ID: ISSN 1474-9718

Publisher:

Anatomical Society - Wiley

Country of Publication:

United States

Language:

English

Subject:

59 BASIC BIOLOGICAL SCIENCES; Cell Biology; Geriatrics & Gerontology; aging; cellular senescence; cytokines; single cell; transcriptomics