학술논문

Unmasking Transcriptional Heterogeneity in Senescent Cells
Document Type
article
Source
Current Biology. 27(17)
Subject
Biochemistry and Cell Biology
Biological Sciences
Genetics
Aging
Aetiology
2.1 Biological and endogenous factors
Animals
Cell Line
Cellular Senescence
Humans
Rats
Transcriptome
DNA damage
RNA-seq
SASP
cell-cycle arrest
cellular senescence
primary cells
qPCR
transcriptional signatures
tumor suppression
whole-transcriptome sequencing
Medical and Health Sciences
Psychology and Cognitive Sciences
Developmental Biology
Biological sciences
Biomedical and clinical sciences
Psychology
Language
Abstract
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 [5-8], 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.