Evidence map›Paper›PMID 34230586›Full record

ArticleScientific reports2021

Genome-wide CRISPR/Cas9 screening in human iPS derived cardiomyocytes uncovers novel mediators of doxorubicin cardiotoxicity.

Valerie Sapp, Aitor Aguirre, Gayatri Mainkar, Jeffrey Ding, Eric Adler, Ronglih Liao, Sonia Sharma, Mohit Jain

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
4.5field-weighted citation impact, top 4% of its field
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

25 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
  2. Impact of CaInternational journal of molecular sciences · 2026
    Review
  3. Review
  4. CRISPR and the Future of Cardiac Disease Therapy: A New Genetic Frontier.International journal of molecular sciences · 2026
    Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Review
  19. CRISPR screening in cardiovascular research.Frontiers in cell and developmental biology · 2023
    Review
  20. Functional genomics in stem cell models: considerations and applications.Frontiers in cell and developmental biology · 2023
    Review
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

8 authors at 4 institutions in 1 country.

Valerie SappDepartment of Medicine, University of California, San Diego, San Diego, CA, USA.
Aitor AguirreDepartment of Medicine, University of California, San Diego, San Diego, CA, USA.
Gayatri MainkarDepartment of Medicine, University of California, San Diego, San Diego, CA, USA.
Jeffrey DingDepartment of Medicine, University of California, San Diego, San Diego, CA, USA.
Eric AdlerDepartment of Medicine, University of California, San Diego, San Diego, CA, USA.
Ronglih LiaoDepartment of Medicine, Stanford University, Palo Alto, USA.
Sonia SharmaLa Jolla Institute for Immunology, San Diego, CA, USA.
Mohit JainDepartment of Medicine, University of California, San Diego, San Diego, CA, USA. mjain@health.ucsd.edu.
University of California, San Diego · USLa Jolla Institute for Immunology · USMichigan State University · USStanford University · US

Funding

GRADUATE TRAINING IN CELLULAR &MOLECULAR PHARMACOLOGYT32GM007752 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BROWN, JOAN HELLER, HANDEL, TRACY M · 1985 to 2023
$13.5M
U of Calif, San Diego Neuroscience Microscopy ImagingP30NS047101 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, ZHENG, BINHAI · 2003 to 2022
$9.0M
Mapping the Plasma Exposome and its Association with Human Cardiovascular DiseaseR01ES027595 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JAIN, MOHIT · 2017 to 2021
$3.3M
Mulan: a novel regulator of mitochondrial dynamics, mitophagy and heart functionR01HL132511 · NHLBI · STANFORD UNIVERSITY · PI LIAO, RONGLIH, ZERVOS, ANTONIS S · 2017 to 2020
$2.8M
Metabolic underpinnings of AL amyloid cardiomyopathyR01HL128135 · NHLBI · STANFORD UNIVERSITY · PI LIAO, RONGLIH · 2015 to 2018
$2.5M
Targeting tumor endothelium for cancer surveillance and immunotherapyR01CA199376 · NCI · LA JOLLA INSTITUTE FOR IMMUNOLOGY · PI SHARMA, SONIA · 2015 to 2019
$2.0M
Lipid signaling in cardiac development and diseaseK01HL135464 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI AGUIRRE, AITOR · 2017 to 2021
$795k
Induced Pluripotent Stem Cells for the Study of Long QT SyndromeK23HL107755 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ADLER, ERIC DAVID · 2011 to 2015
$672k
RapidFire mass spectrometry systemS10OD020025 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JAIN, MOHIT · 2015 to 2015
$600k
Mapping metabolic activities in stem cell-derived models of human cardiomyopathyR03HL133720 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JAIN, MOHIT · 2016 to 2017
$155k
NHLBI NIH HHS R01 HL132511NIEHS NIH HHS R01 ES027595NIH HHS K01HL135464NIH HHS K23HL107755NIH HHS R01CA199376NIH HHS R01HL128135NIH HHS R03HL133720NIH HHS S10 OD020025NIH HHS T32GM007752NINDS NIH HHS P30 NS047101
6 · The paper itself

Abstract

Human induced pluripotent stem (iPS) cell technologies coupled with genetic engineering now facilitate the study of the molecular underpinnings of disease in relevant human cell types. Application of CRISPR/Cas9-based approaches for genome-scale functional screening in iPS-derived cells, however, has been limited by technical constraints, including inefficient transduction in pooled format, loss of library representation, and poor cellular differentiation. Herein, we present optimized approaches for whole-genome CRISPR/Cas9 based screening in human iPS derived cardiomyocytes with near genome-wide representation at both the iPS and differentiated cell stages. As proof-of-concept, we perform a screen to investigate mechanisms underlying doxorubicin mediated cell death in iPS derived cardiomyocytes. We identified two poorly characterized, human-specific transporters (SLCO1A2, SLCO1B3) whose loss of function protects against doxorubicin-cardiotoxicity, but does not affect cell death in cancer cells. This study provides a technical framework for genome-wide functional screening in iPS derived cells and identifies new targets to mitigate doxorubicin-cardiotoxicity in humans.

Indexed as

Genome, HumanCardiotoxicityCell Line, TumorCRISPR-Cas SystemsDoxorubicinHumansInduced Pluripotent Stem CellsLentivirusMyocytes, CardiacPhenotypeRNA, Guide, CRISPR-Cas SystemsDoxorubicinRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID34230586
PMCPMC8260754
OpenAlexW3179677353

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.