Profiling the Non-genetic Origins of Cancer Drug Resistance with a Single-Cell Functional Genomics Approach Using Predictive Cell Dynamics.
Apoptosis
/ drug effects
Biomarkers, Pharmacological
/ analysis
Cell Line, Tumor
Drug Resistance, Neoplasm
/ physiology
Gene Expression Regulation, Neoplastic
/ drug effects
Genomics
HeLa Cells
Humans
Neoplasms
/ genetics
Single-Cell Analysis
/ methods
TNF-Related Apoptosis-Inducing Ligand
/ genetics
cancer drug resistance
cell-to-cell variability
laser-capture microdissection
live-cell microscopy
pharmacogenomics
single-cell
systems biology
transcriptomics
Journal
Cell systems
ISSN: 2405-4720
Titre abrégé: Cell Syst
Pays: United States
ID NLM: 101656080
Informations de publication
Date de publication:
21 10 2020
21 10 2020
Historique:
received:
02
03
2020
revised:
12
06
2020
accepted:
28
08
2020
entrez:
25
10
2020
pubmed:
26
10
2020
medline:
31
8
2021
Statut:
ppublish
Résumé
Non-genetic heterogeneity observed in clonal cell populations is an immediate cause of drug resistance that remains challenging to profile because of its transient nature. Here, we coupled three single-cell technologies to link the predicted drug response of a cell to its own genome-wide transcriptomic profile. As a proof of principle, we analyzed the response to tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) in HeLa cells to demonstrate that cell dynamics can discriminate the transient transcriptional states at the origin of cell decisions such as sensitivity and resistance. Our same-cell approach, named fate-seq, can reveal the molecular factors regulating the efficacy of a drug in clonal cells, providing therapeutic targets of non-genetic drug resistance otherwise confounded in gene expression noise. A record of this paper's transparent peer review process is included in the Supplemental Information.
Identifiants
pubmed: 33099406
pii: S2405-4712(20)30330-6
doi: 10.1016/j.cels.2020.08.019
pii:
doi:
Substances chimiques
Biomarkers, Pharmacological
0
TNF-Related Apoptosis-Inducing Ligand
0
TNFSF10 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
367-374.e5Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests Methods and results presented here are part of a patent application (J.R., A.P., L.C.G.-P., and M.M.). Other authors declare no competing interests.