Evidence map›Paper›PMID 26543098›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2016

Genome-Edited Human Pluripotent Stem Cell-Derived Macrophages as a Model of Reverse Cholesterol Transport--Brief Report.

Rajat M Gupta, Torsten B Meissner, Chad A Cowan, Kiran Musunuru

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
7.7field-weighted citation impact, top 2% 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

18 citing papers in PubMed, 36 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Reporting Sex and Sex Differences in Preclinical Studies.Arteriosclerosis, thrombosis, and vascular biology · 2018
    Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Genome Editing: The Recent History and Perspective in Cardiovascular Diseases.Journal of the American College of Cardiology · 2017
    Review
  11. Article
  12. Review
  13. Article
  14. Review
  15. Genome editing in cardiovascular diseases.Nature reviews. Cardiology · 2017
    Review
  16. Article
  17. Site-Specific Genome Engineering in Human Pluripotent Stem Cells.International journal of molecular sciences · 2016
    Review
  18. Human Macrophage Genetic Engineering.Arteriosclerosis, thrombosis, and vascular biology · 2016
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Rajat M GuptaFrom the Department of Stem Cell and Regenerative Biology, Harvard University, and Harvard Stem Cell Institute, Cambridge, MA (R.M.G., T.B.M., C.A.C., K.M.); and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (R.M.G., K.M.).
Torsten B MeissnerFrom the Department of Stem Cell and Regenerative Biology, Harvard University, and Harvard Stem Cell Institute, Cambridge, MA (R.M.G., T.B.M., C.A.C., K.M.); and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (R.M.G., K.M.).
Chad A Cowan
Kiran Musunuru
Brigham and Women's Hospital · USHarvard Stem Cell Institute · US

Funding

Isogenic Human Pluripotent Stem Cell-Based Models of Human Disease MutationsR01DK097768 · NIDDK · BROAD INSTITUTE, INC. · PI COWAN, CHAD ALBERT, ZHANG, FENG · 2012 to 2016
$11.0M
Systematic cell-based functional screening for LDL and triglyceride genesR21HL120781 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI COWAN, CHAD ALBERT, KATHIRESAN, SEKAR · 2014 to 2015
$473k
NHLBI NIH HHS R21 HL120781NIDDK NIH HHS R01 DK097768
6 · The paper itself

Abstract

objectiveTo create isogenic human pluripotent stem cell-derived macrophages with and without ABCA1 expression as a model for reverse cholesterol transport. APPROACH AND

resultsThe clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) genome-editing system was used to introduce frameshift mutations into the coding sequence of ATP-binding cassette, subfamily A, member 1. Individual human pluripotent stem cell clones with deleterious mutations were identified, expanded, and differentiated into mature macrophages with a cytokine-based, feeder-free differentiation protocol. Wild-type cells demonstrated effective cholesterol efflux to apoAI acceptor, whereas ABCA1(-/-) cells displayed significantly reduced efflux ability and increased expression of proinflammatory cytokines.

conclusionsHuman pluripotent stem cell-derived macrophages capable of reverse cholesterol transport can be rapidly generated and genetically edited with CRISPR/Cas9. Introduction of homozygous frameshift mutations results in loss of ABCA1 expression in differentiated macrophages and subsequent reduction of cholesterol efflux capability. This facile genome-editing approach and differentiation protocol pave the way for future studies of the molecular determinants of reverse cholesterol transport and other macrophage properties.

Indexed as

Genome, HumanApolipoprotein A-IATP Binding Cassette Transporter 1Biological TransportCell DifferentiationCell LineCholesterolCRISPR-Associated ProteinsCRISPR-Cas SystemsCytokinesFrameshift MutationGene Expression RegulationGenotypeHumansINDEL MutationInflammation MediatorsABCA1 protein, humanAPOA1 protein, humanApolipoprotein A-IATP Binding Cassette Transporter 1CholesterolCRISPR-Associated ProteinsCytokinesInflammation Mediatorscell differentiationcholesterolgeneticsmacrophagesstem cells

Identifiers

PMID26543098
PMCPMC4690765
OpenAlexW2213238510

What OpenQuestion holds

Textmetadata
LicenceTDM
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.