Evidence map›Paper›PMID 28781079›Full record

ArticleStem cell reports2017

Rapid Generation of Human Genetic Loss-of-Function iPSC Lines by Simultaneous Reprogramming and Gene Editing.

Andrew M Tidball, Louis T Dang, Trevor W Glenn, Emma G Kilbane, Daniel J Klarr, Joshua L Margolis, Michael D Uhler, Jack M Parent

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

Article in Stem cell reports, 2017. 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
2.1field-weighted citation impact, top 12% 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, 48 citations in OpenAlex.

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  18. CHD2-Related CNS Pathologies.International journal of molecular sciences · 2021
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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 2 institutions in 1 country.

Andrew M TidballDepartment of Neurology, University of Michigan Medical School, 5021 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.
Louis T DangDepartment of Pediatrics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Trevor W GlennDepartment of Neurology, University of Michigan Medical School, 5021 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.
Emma G KilbaneDepartment of Neurology, University of Michigan Medical School, 5021 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.
Daniel J KlarrDepartment of Neurology, University of Michigan Medical School, 5021 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.
Joshua L MargolisDepartment of Neurology, University of Michigan Medical School, 5021 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA.
Michael D UhlerDepartment of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Molecular and Behavioral Neuroscience Institute, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Jack M ParentDepartment of Neurology, University of Michigan Medical School, 5021 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200, USA; VA Ann Arbor HealthCare System, Ann Arbor, MI 48105, USA. Electronic address: parent@umich.edu.
University of Michigan–Ann Arbor · USVA Ann Arbor Healthcare System · US

Funding

Advancing Child Health Through Cellular and Molecular BiologyK12HD028820 · NICHD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Donna M. Martin · 2002 to 2026
$9.2M
SUDEP Research Alliance: iPSC and Mouse Neurocardiac Models, Application 6 of 7U01NS090364 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ISOM, LORI L., PARENT, JACK M · 2014 to 2018
$3.3M
NICHD NIH HHS K12 HD028820NINDS NIH HHS U01 NS090364
6 · The paper itself

Abstract

Specifically ablating genes in human induced pluripotent stem cells (iPSCs) allows for studies of gene function as well as disease mechanisms in disorders caused by loss-of-function (LOF) mutations. While techniques exist for engineering such lines, we have developed and rigorously validated a method of simultaneous iPSC reprogramming while generating CRISPR/Cas9-dependent insertions/deletions (indels). This approach allows for the efficient and rapid formation of genetic LOF human disease cell models with isogenic controls. The rate of mutagenized lines was strikingly consistent across experiments targeting four different human epileptic encephalopathy genes and a metabolic enzyme-encoding gene, and was more efficient and consistent than using CRISPR gene editing of established iPSC lines. The ability of our streamlined method to reproducibly generate heterozygous and homozygous LOF iPSC lines with passage-matched isogenic controls in a single step provides for the rapid development of LOF disease models with ideal control lines, even in the absence of patient tissue.

Indexed as

Gene EditingCell LineCellular ReprogrammingCRISPR-Cas SystemsGenetic HeterogeneityGenomic InstabilityGenotypeHumansINDEL MutationInduced Pluripotent Stem CellsLoss of Function MutationReproducibility of ResultsRNA, Guide, CRISPR-Cas SystemsRNA, Guide, CRISPR-Cas SystemsCRISPR/Cas9epileptic encephalopathygene editinggenetic epilepsyinduced pluripotent stem cellsreprogramming

Identifiers

PMID28781079
PMCPMC5599229
OpenAlexW2742496349

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.