Evidence map›Paper›PMID 25339441›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Single-cell analyses of transcriptional heterogeneity during drug tolerance transition in cancer cells by RNA sequencing.

Mei-Chong Wendy Lee, Fernando J Lopez-Diaz, Shahid Yar Khan, Muhammad Akram Tariq, Yelena Dayn, Charles Joseph Vaske, Amie J Radenbaugh, Hyunsung John Kim, Beverly M Emerson, Nader Pourmand

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
103citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

103 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
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  5. Article
  6. Review
  7. Review
  8. Purinergic CaCancers · 2024
    Article
  9. Review
  10. Purinergic CabioRxiv : the preprint server for biology · 2024
    Article
  11. Review
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43 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Mei-Chong Wendy LeeBiomolecular Engineering Department, University of California, Santa Cruz, CA 95064;
Fernando J Lopez-DiazLaboratory of Regulatory Biology, The Salk Institute for Biological Studies, La Jolla, CA 92037;
Shahid Yar KhanBiomolecular Engineering Department, University of California, Santa Cruz, CA 95064;
Muhammad Akram TariqBiomolecular Engineering Department, University of California, Santa Cruz, CA 95064;
Yelena DaynTransgenic Core Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037; and.
Charles Joseph VaskeFive3 Genomics, LLC, Santa Cruz, CA 95060.
Amie J RadenbaughBiomolecular Engineering Department, University of California, Santa Cruz, CA 95064;
Hyunsung John KimBiomolecular Engineering Department, University of California, Santa Cruz, CA 95064;
Beverly M EmersonLaboratory of Regulatory Biology, The Salk Institute for Biological Studies, La Jolla, CA 92037; pourmand@soe.ucsc.edu emerson@salk.edu.
Nader PourmandBiomolecular Engineering Department, University of California, Santa Cruz, CA 95064; pourmand@soe.ucsc.edu emerson@salk.edu.

Funding

WHOLE YEAST GENOME TRANSCRIPTIONAL AND FUNCTIONAL GENE MAPS--A FEASIBILITY STUDYP01HG000205 · NHGRI · STANFORD UNIVERSITY · PI HOWE, ROGER THOMAS, JI, HANLEE P · 1990 to 2016
$120.9M
Viral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Ye Zheng · 1985 to 2026
$82.8M
TRANS_NETWORK PROJECTSU54CA143803 · NCI · PRINCETON UNIVERSITY · PI TLSTY, THEA D · 2009 to 2013
$14.2M
A NEW ES CELL DELETION RESOURCE AND WILLIAMS SYNDROMEF32HG000205 · NHGRI · JACKSON LABORATORY · PI GOODWIN, NEAL C · 1999 to 1999
–
NCI NIH HHS P30 CA014195NCI NIH HHS P30CA014195NCI NIH HHS U54 CA143803NCI NIH HHS U54CA143803NHGRI NIH HHS F32 HG000205NHGRI NIH HHS P01-35HG000205NHGRI NIH HHS P01 HG000205
6 · The paper itself

Abstract

The acute cellular response to stress generates a subpopulation of reversibly stress-tolerant cells under conditions that are lethal to the majority of the population. Stress tolerance is attributed to heterogeneity of gene expression within the population to ensure survival of a minority. We performed whole transcriptome sequencing analyses of metastatic human breast cancer cells subjected to the chemotherapeutic agent paclitaxel at the single-cell and population levels. Here we show that specific transcriptional programs are enacted within untreated, stressed, and drug-tolerant cell groups while generating high heterogeneity between single cells within and between groups. We further demonstrate that drug-tolerant cells contain specific RNA variants residing in genes involved in microtubule organization and stabilization, as well as cell adhesion and cell surface signaling. In addition, the gene expression profile of drug-tolerant cells is similar to that of untreated cells within a few doublings. Thus, single-cell analyses reveal the dynamics of the stress response in terms of cell-specific RNA variants driving heterogeneity, the survival of a minority population through generation of specific RNA variants, and the efficient reconversion of stress-tolerant cells back to normalcy.

Indexed as

Breast NeoplasmsDrug Resistance, NeoplasmRNA, NeoplasmSequence Analysis, RNATranscription, GeneticAntineoplastic Agents, PhytogenicCell Line, TumorFemaleHumansPaclitaxelAntineoplastic Agents, PhytogenicPaclitaxelRNA, Neoplasmdrug resistancepaclitaxelRNA-Seqsingle celltumor heterogeniety

Identifiers

PMID25339441
PMCPMC4226127

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.