Evidence map›Paper›PMID 31759059›Full record

ArticleGastroenterology2020

A High-Content Screen Identifies MicroRNAs That Regulate Liver Repopulation After Injury in Mice.

Adam M Zahm, Amber W Wang, Yue J Wang, Jonathan Schug, Kirk J Wangensteen, Klaus H Kaestner

Open access · greenAbstract read
In one paragraph

Article in Gastroenterology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

8 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Article
  6. Article
  7. Genetic and Cellular Contributions to Liver Regeneration.Cold Spring Harbor perspectives in biology · 2021
    Article
  8. Article
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

6 authors at 2 institutions in 1 country.

Adam M ZahmDepartment of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania.
Amber W WangDepartment of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania.
Yue J WangDepartment of Biomedical Sciences, Florida State University, Tallahassee, Florida.
Jonathan SchugDepartment of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania.
Kirk J WangensteenDepartment of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: wkirk@pennmedicine.upenn.edu.
Klaus H KaestnerDepartment of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: kaestner@pennmedicine.upenn.edu.
University of Pennsylvania · USFlorida State University · US

Funding

VIRAL VECTOR COREP30DK019525 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI DOUGLAS J EPSTEIN · 1986 to 2026
$48.3M
TRANSGENIC AND CHIMERIC MOUSE COREP30DK050306 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI GARY D. WU · 1997 to 2026
$32.5M
Innovative Genetic Approaches to Enhance Liver Repopulation and Reduce Cancer Risk and ProgressionR01CA249929 · NCI · UNIVERSITY OF PENNSYLVANIA · PI KAESTNER, KLAUS H · 2020 to 2024
$2.7M
Innovative Genetic Approaches for Hepatic RepopulationR01DK102667 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI KAESTNER, KLAUS H · 2015 to 2019
$1.8M
Genetic basis of liver repopulationK08DK106478 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI WANGENSTEEN, KIRK J · 2015 to 2019
$787k
Role of microRNAs in pediatric inflammatory bowel diseaseK01DK102868 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI ZAHM, ADAM MATTHEW · 2015 to 2019
$665k
Elucidating Redox Regulation in the Repopulating LiverF31DK113666 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI WANG, AMBER WEICHING · 2017 to 2019
$94k
NCI NIH HHS R01 CA249929NIDDK NIH HHS F31 DK113666NIDDK NIH HHS K01 DK102868NIDDK NIH HHS K08 DK106478NIDDK NIH HHS P30 DK019525NIDDK NIH HHS P30 DK050306NIDDK NIH HHS R01 DK102667
6 · The paper itself

Abstract

BACKGROUND &

aimsLiver regeneration is impaired in mice with hepatocyte-specific deficiencies in microRNA (miRNA) processing, but it is not clear which miRNAs regulate this process. We developed a high-throughput screen to identify miRNAs that regulate hepatocyte repopulation after toxic liver injury using fumarylacetoacetate hydrolase-deficient mice.

methodsWe constructed plasmid pools encoding more than 30,000 tough decoy miRNA inhibitors (hairpin nucleic acids designed to specifically inhibit interactions between miRNAs and their targets) to target hepatocyte miRNAs in a pairwise manner. The plasmid libraries were delivered to hepatocytes in fumarylacetoacetate hydrolase-deficient mice at the time of liver injury via hydrodynamic tail-vein injection. Integrated transgene-containing transposons were quantified after liver repopulation via high-throughput sequencing. Changes in polysome-bound transcripts after miRNA inhibition were determined using translating ribosome affinity purification followed by high-throughput sequencing.

resultsAnalyses of tough decoy abundance in hepatocyte genomic DNA and input plasmid pools identified several thousand miRNA inhibitors that were significantly depleted or increased after repopulation. We classified a subset of miRNA binding sites as those that have strong effects on liver repopulation, implicating the targeted hepatocyte miRNAs as regulators of this process. We then generated a high-content map of pairwise interactions between 171 miRNA-binding sites and identified synergistic and redundant effects.

conclusionsWe developed a screen to identify miRNAs that regulate liver repopulation after injury in live mice.

Indexed as

AnimalsChromosome MappingHepatocytesHigh-Throughput Nucleotide SequencingHydrolasesLiverLiver RegenerationMiceMicroRNAsPlasmidsRNA-Binding ProteinsfumarylacetoacetaseHydrolasesMicroRNAsRNA-Binding ProteinsGenetic ScreenmicroRNAPost-Transcriptional RegulationTough decoy

Identifiers

PMID31759059
PMCPMC7472793
OpenAlexW2990796202

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.