Evidence map›Paper›PMID 27586271›Full record

ArticleBiochemical and biophysical research communications2016

Differential effects of toll-like receptor stimulation on mRNA-driven myogenic conversion of human and mouse fibroblasts.

Jaewoo Lee, Li Xu, Tyler M Gibson, Charles A Gersbach, Bruce A Sullenger

Abstract read
In one paragraph

Article in Biochemical and biophysical research communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.7field-weighted citation impact, top 25% 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

6 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
  2. Article
  3. Concentration of NaScientific reports · 2021
    Article
  4. Review
  5. mRNA-Based Genetic Reprogramming.Molecular therapy : the journal of the American Society of Gene Therapy · 2019
    Review
  6. Review
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

5 authors at 2 institutions in 1 country.

Jaewoo LeeDepartment of Surgery, Duke University, USA; Duke Translational Research Institute, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: jaewoo.lee@duke.edu.
Li XuDepartment of Surgery, Duke University, USA.
Tyler M GibsonDepartment of Biomedical Engineering, Duke University, USA.
Charles A GersbachDepartment of Biomedical Engineering, Duke University, USA.
Bruce A SullengerDepartment of Surgery, Duke University, USA; Duke Translational Research Institute, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: bruce.sullenger@duke.edu.
Duke University · USDuke Medical Center · US

Funding

University Training Program in Biomolecular & Tissue EngineeringT32GM008555 · NIGMS · DUKE UNIVERSITY · PI GERSBACH, CHARLES A. · 1994 to 2021
$8.1M
Engineering Morphogenetic Factors for Enhanced Genetic ReprogrammingDP2OD008586 · OD · DUKE UNIVERSITY · PI GERSBACH, CHARLES A. · 2011 to 2011
$2.4M
NIGMS NIH HHS T32 GM008555NIH HHS DP2 OD008586
6 · The paper itself

Abstract

Transfection with in vitro transcribed mRNAs is a safe and effective tool to convert somatic cells to any cell type of interest. One caveat of mRNA transfection is that mRNAs are recognized by multiple RNA-sensing toll like receptors (TLRs). These TLRs can both promote and inhibit cellular reprogramming. We demonstrated that mRNA transfection stimulated TLR3 and TLR7 and induced cytotoxicity and IFN-β expression in human and mouse fibroblasts. Furthermore, mRNA transfection induced paracrine inhibition of repeated mRNA transfection through type I IFNs. Modified mRNAs (mmRNAs) containing pseudouridine and 5-methycytosine reduced TLR stimulation, cytotoxicity and IFN-β expression in fibroblasts. Repeated liposomal transfection with MyoD mmRNAs significantly enhanced myogenic conversion of human and mouse fibroblasts compared with repeated transfection with MyoD mRNAs. Interestingly, electroporation of mRNAs and mmRNAs completely abrogated cytotoxicity and IFN-β expression and also abolished myogenic conversion of fibroblasts. At a low concentration, TLR7/8 agonist R848 enhanced MyoD mmRNA-driven conversion of human fibroblasts into skeletal muscle cells, whereas high concentrations of R848 inhibited myogenic conversion of fibroblasts. Our study suggests that deliberate control of TLR signaling is a key factor in the success of mRNA-driven cellular reprogramming.

Indexed as

Muscle DevelopmentAnimalsCell DeathElectroporationFibroblastsHumansInfant, NewbornInterferon-betaMiceMyoD ProteinParacrine CommunicationRNA, MessengerSignal TransductionToll-Like Receptor 3Toll-Like Receptor 7Transcription, GeneticInterferon-betaMyoD ProteinRNA, MessengerToll-Like Receptor 3Toll-Like Receptor 7InterferonmRNAReprogrammingToll-like receptorTransdifferentiationTransfection

Identifiers

PMID27586271
PMCPMC6044724
OpenAlexW2513096418

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.