Current Biology
Volume 27, Issue 17, 11 September 2017, Pages 2652-2660.e4
Journal home page for Current Biology

Report
Unmasking Transcriptional Heterogeneity in Senescent Cells

https://doi.org/10.1016/j.cub.2017.07.033Get rights and content
Under an Elsevier user license
open archive

Highlights

  • The transcriptome of senescent cells is highly heterogeneous

  • Senescence transcriptome programs depend on the cell type and stress

  • Gene expression in senescent cells is temporally dynamic

  • We identified 55 genes at the core of the senescence-associated transcriptome

Summary

Cellular senescence is a state of irreversibly arrested proliferation, often induced by genotoxic stress [1]. Senescent cells participate in a variety of physiological and pathological conditions, including tumor suppression [2], embryonic development [3, 4], tissue repair [5, 6, 7, 8], and organismal aging [9]. The senescence program is variably characterized by several non-exclusive markers, including constitutive DNA damage response (DDR) signaling, senescence-associated β-galactosidase (SA-βgal) activity, increased expression of the cyclin-dependent kinase (CDK) inhibitors p16INK4A (CDKN2A) and p21CIP1 (CDKN1A), increased secretion of many bio-active factors (the senescence-associated secretory phenotype, or SASP), and reduced expression of the nuclear lamina protein LaminB1 (LMNB1) [1]. Many senescence-associated markers result from altered transcription, but the senescent phenotype is variable, and methods for clearly identifying senescent cells are lacking [10]. Here, we characterize the heterogeneity of the senescence program using numerous whole-transcriptome datasets generated by us or publicly available. We identify transcriptome signatures associated with specific senescence-inducing stresses or senescent cell types and identify and validate genes that are commonly differentially regulated. We also show that the senescent phenotype is dynamic, changing at varying intervals after senescence induction. Identifying novel transcriptome signatures to detect any type of senescent cell or to discriminate among diverse senescence programs is an attractive strategy for determining the diverse biological roles of senescent cells and developing specific drug targets.

Keywords

cellular senescence
SASP
DNA damage
primary cells
whole-transcriptome sequencing
qPCR
transcriptional signatures
cell-cycle arrest
RNA-seq
tumor suppression

Cited by (0)

4

Lead Contact