Evidence map›Paper›PMID 27355827›Full record

ArticlePloS one2016

A Conserved MicroRNA Regulatory Circuit Is Differentially Controlled during Limb/Appendage Regeneration.

Benjamin L King, Viravuth P Yin

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
5.4field-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

31 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.

  1. Material-Assisted Strategies for Osteochondral Defect Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022
    Pooled it
  2. Article
  3. MicroRNAs in Tissue Regeneration: Lessons from Animal Models.International journal of molecular sciences · 2025
    Review
  4. Article
  5. Article
  6. Review
  7. Expression Analysis ofInternational journal of molecular sciences · 2022
    Article
  8. Review
  9. Review
  10. Review
  11. Article
  12. BCL2L13: physiological and pathological meanings.Cellular and molecular life sciences : CMLS · 2021
    Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. A Tale of Two States: Normal and Transformed, With and Without Rigidity Sensing.Annual review of cell and developmental biology · 2019
    Review
  18. Article
  19. High-depth transcriptomic profiling reveals the temporal gene signature of human mesenchymal stem cells during chondrogenesis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
    Article
  20. 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

2 authors at 1 institution in 1 country.

Benjamin L KingKathryn W. Davis Center for Regenerative Biology and Medicine, Mount Desert Island, Biological Laboratory, Salisbury Cove, Maine, United States of America.
Viravuth P YinKathryn W. Davis Center for Regenerative Biology and Medicine, Mount Desert Island, Biological Laboratory, Salisbury Cove, Maine, United States of America.
University of Maine · US

Funding

The Maine Biomedical Research Network (INBRE)P20GM103423 · NIGMS · MOUNT DESERT ISLAND BIOLOGICAL LAB · PI Dustin Lynn Updike · 2012 to 2026
$60.0M
Understanding the role of thyroid hormone signaling during axolotl limb regenerationP20GM104318 · NIGMS · MOUNT DESERT ISLAND BIOLOGICAL LAB · PI DRUMMOND, IAIN A. · 2013 to 2023
$23.0M
NIGMS NIH HHS P20 GM103423NIGMS NIH HHS P20 GM104318
6 · The paper itself

Abstract

backgroundAlthough regenerative capacity is evident throughout the animal kingdom, it is not equally distributed throughout evolution. For instance, complex limb/appendage regeneration is muted in mammals but enhanced in amphibians and teleosts. The defining characteristic of limb/appendage regenerative systems is the formation of a dedifferentiated tissue, termed blastema, which serves as the progenitor reservoir for regenerating tissues. In order to identify a genetic signature that accompanies blastema formation, we employ next-generation sequencing to identify shared, differentially regulated mRNAs and noncoding RNAs in three different, highly regenerative animal systems: zebrafish caudal fins, bichir pectoral fins and axolotl forelimbs.

resultsThese studies identified a core group of 5 microRNAs (miRNAs) that were commonly upregulated and 5 miRNAs that were commonly downregulated, as well as 4 novel tRNAs fragments with sequences conserved with humans. To understand the potential function of these miRNAs, we built a network of 1,550 commonly differentially expressed mRNAs that had functional relationships to 11 orthologous blastema-associated genes. As miR-21 was the most highly upregulated and most highly expressed miRNA in all three models, we validated the expression of known target genes, including the tumor suppressor, pdcd4, and TGFβ receptor subunit, tgfbr2 and novel putative target genes such as the anti-apoptotic factor, bcl2l13, Choline kinase alpha, chka and the regulator of G-protein signaling, rgs5.

conclusionsOur extensive analysis of RNA-seq transcriptome profiling studies in three regenerative animal models, that diverged in evolution ~420 million years ago, reveals a common miRNA-regulated genetic network of blastema genes. These comparative studies extend our current understanding of limb/appendage regeneration by identifying previously unassociated blastema genes and the extensive regulation by miRNAs, which could serve as a foundation for future functional studies to examine the process of natural cellular reprogramming in an injury context.

Indexed as

Gene Regulatory NetworksAmbystoma mexicanumAnimal FinsAnimalsExtremitiesFishesGene Expression ProfilingGene Expression Regulation, DevelopmentalHigh-Throughput Nucleotide SequencingMicroRNAsRegenerationRNA, UntranslatedSequence Analysis, RNASignal TransductionZebrafishMicroRNAsRNA, Untranslated

Identifiers

PMID27355827
PMCPMC4927183
OpenAlexW2468572787

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.