Evidence map›Paper›PMID 33452356›Full record

ArticleScientific reports2021

A quantitative model of cellular decision making in direct neuronal reprogramming.

Adriaan Merlevede, Emilie M Legault, Viktor Drugge, Roger A Barker, Janelle Drouin-Ouellet, Victor Olariu

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.6field-weighted citation impact, top 37% 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

4 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. 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

6 authors at 3 institutions in 3 countries.

Adriaan MerlevedeComputational Biology and Biological Physics, Department of Astronomy and Theoretical Physics, Lund University, 223 62, Lund, Sweden.
Emilie M LegaultFaculté de Pharmacie, Université de Montréal, Montreal, QC, H3T 1J4, Canada.
Viktor DruggeComputational Biology and Biological Physics, Department of Astronomy and Theoretical Physics, Lund University, 223 62, Lund, Sweden.
Roger A BarkerCambridge Centre for Brain Repair, University of Cambridge, Forvie Site, Robinson Way, Cambridge, CB2 2PY, UK.
Janelle Drouin-OuelletFaculté de Pharmacie, Université de Montréal, Montreal, QC, H3T 1J4, Canada. janelle.drouin-ouellet@umontreal.ca.
Victor OlariuComputational Biology and Biological Physics, Department of Astronomy and Theoretical Physics, Lund University, 223 62, Lund, Sweden. victor.olariu@thep.lu.se.
Lund University · SEUniversité de Montréal · CAUniversity of Cambridge · GB

Funding

Kinetic modeling and single-cell molecular mechanisms of early T-cell commitmentR01HL119102 · NHLBI · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI PETERSON, CARSTEN, ROTHENBERG, ELLEN V. · 2014 to 2018
$3.0M
Medical Research Council MC_PC_17230NHLBI NIH HHS R01 HL119102
6 · The paper itself

Abstract

The direct reprogramming of adult skin fibroblasts to neurons is thought to be controlled by a small set of interacting gene regulators. Here, we investigate how the interaction dynamics between these regulating factors coordinate cellular decision making in direct neuronal reprogramming. We put forward a quantitative model of the governing gene regulatory system, supported by measurements of mRNA expression. We found that nPTB needs to feed back into the direct neural conversion network most likely via PTB in order to accurately capture quantitative gene interaction dynamics and correctly predict the outcome of various overexpression and knockdown experiments. This was experimentally validated by nPTB knockdown leading to successful neural conversion. We also proposed a novel analytical technique to dissect system behaviour and reveal the influence of individual factors on resulting gene expression. Overall, we demonstrate that computational analysis is a powerful tool for understanding the mechanisms of direct (neuronal) reprogramming, paving the way for future models that can help improve cell conversion strategies.

Indexed as

AgedCellular ReprogrammingCellular Reprogramming TechniquesComputational BiologyFemaleFibroblastsGene ExpressionGene Expression RegulationGene Regulatory NetworksHumansMiddle AgedModels, TheoreticalNerve Tissue ProteinsNeuronsPolypyrimidine Tract-Binding ProteinPrimary Cell CultureNerve Tissue ProteinsPolypyrimidine Tract-Binding ProteinTranscription Factors

Identifiers

PMID33452356
PMCPMC7810861
OpenAlexW3025861554

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.