Evidence map›Paper›PMID 22967807›Full record

ArticleCirculation research2012

Genome editing of human embryonic stem cells and induced pluripotent stem cells with zinc finger nucleases for cellular imaging.

Yongming Wang, Wendy Y Zhang, Shijun Hu, Feng Lan, Andrew S Lee, Bruno Huber, Leszek Lisowski, Ping Liang, Mei Huang, Patricia E de Almeida and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Circulation research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
4.4field-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

59 citing papers in PubMed, 102 citations in OpenAlex.

  1. Article
  2. Gene editing enables non-invasiveMolecular therapy. Methods & clinical development · 2025
    Article
  3. Review
  4. Review
  5. Review
  6. Frontiers in cardiovascular medicine · 2023
    Article
  7. hPSC gene editing for cardiac disease therapy.Pflugers Archiv : European journal of physiology · 2022
    Review
  8. Article
  9. Article
  10. Compact SchCas9 Recognizes the Simple NNGR PAM.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022
    Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Non-invasive Reporter Gene Imaging of Cell Therapies, including T Cells and Stem Cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2020
    Review
  19. Article
  20. Characterization ofFrontiers in cell and developmental biology · 2020
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 1 institution in 1 country.

Yongming WangDepartment of Medicine, Division of Cardiology, Stanford School of Medicine, Stanford, CA, USA.
Wendy Y Zhang
Shijun Hu
Feng Lan
Andrew S Lee
Bruno Huber
Leszek Lisowski
Ping Liang
Mei Huang
Patricia E de Almeida
Jong H Won
Ning Sun
Robert C Robbins
Mark A Kay
Fyodor D Urnov
Joseph C Wu
Cardiovascular Institute of the South · US

Funding

Induced pluripotent stem cells in the understanding and treatment of heart diseaseU01HL099776 · NHLBI · STANFORD UNIVERSITY · PI LONGAKER, MICHAEL T, WU, JOSEPH C. · 2009 to 2015
$8.2M
Human Induced Pluripotent Stem Cells for Cardiovascular Disease ModelingR01HL113006 · NHLBI · STANFORD UNIVERSITY · PI WU, JOSEPH C. · 2012 to 2025
$6.8M
Molecular Imaging of Targeted Cardiac Gene TherapyR01HL093172 · NHLBI · STANFORD UNIVERSITY · PI WU, JOSEPH C. · 2009 to 2015
$2.7M
09: Inducing Pluripotency with MiRNAs: New Paradigm Shif in Cell ReprogrammingDP2OD004437 · OD · STANFORD UNIVERSITY · PI WU, JOSEPH C. · 2008 to 2008
$2.4M
Integrated Strategies for Novel Treatment of Myocardial IschemiaR01HL095571 · NHLBI · STANFORD UNIVERSITY · PI WU, JOSEPH C. · 2010 to 2014
$2.0M
Molecular Imaging of Cardiac Stem Cell TherapyR01EB009689 · NIBIB · STANFORD UNIVERSITY · PI WU, JOSEPH C. · 2010 to 2013
$1.4M
NHLBI NIH HHS HL093172NHLBI NIH HHS HL113006NHLBI NIH HHS R01 HL093172NHLBI NIH HHS R01 HL095571NHLBI NIH HHS R01 HL113006NHLBI NIH HHS U01 HL099776NIBIB NIH HHS EB009689NIBIB NIH HHS R01 EB009689NIH HHS DP2 OD004437
6 · The paper itself

Abstract

rationaleMolecular imaging has proven to be a vital tool in the characterization of stem cell behavior in vivo. However, the integration of reporter genes has typically relied on random integration, a method that is associated with unwanted insertional mutagenesis and positional effects on transgene expression.

objectiveTo address this barrier, we used genome editing with zinc finger nuclease (ZFN) technology to integrate reporter genes into a safe harbor gene locus (PPP1R12C, also known as AAVS1) in the genome of human embryonic stem cells and human induced pluripotent stem cells for molecular imaging. METHODS AND

resultsWe used ZFN technology to integrate a construct containing monomeric red fluorescent protein, firefly luciferase, and herpes simplex virus thymidine kinase reporter genes driven by a constitutive ubiquitin promoter into a safe harbor locus for fluorescence imaging, bioluminescence imaging, and positron emission tomography imaging, respectively. High efficiency of ZFN-mediated targeted integration was achieved in both human embryonic stem cells and induced pluripotent stem cells. ZFN-edited cells maintained both pluripotency and long-term reporter gene expression. Functionally, we successfully tracked the survival of ZFN-edited human embryonic stem cells and their differentiated cardiomyocytes and endothelial cells in murine models, demonstrating the use of ZFN-edited cells for preclinical studies in regenerative medicine.

conclusionOur study demonstrates a novel application of ZFN technology to the targeted genetic engineering of human pluripotent stem cells and their progeny for molecular imaging in vitro and in vivo.

Indexed as

AnimalsCell DifferentiationCells, CulturedDeoxyribonucleasesEmbryonic Stem CellsGenes, ReporterGene TargetingGenetic EngineeringGenome, HumanHumansInduced Pluripotent Stem CellsMiceOptical ImagingRNA EditingZinc FingersDeoxyribonucleases

Identifiers

PMID22967807
PMCPMC3518748
OpenAlexW2150582055

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.