Evidence map›Paper›PMID 28646119›Full record

ArticleEMBO molecular medicine2017

REST suppression mediates neural conversion of adult human fibroblasts via microRNA-dependent and -independent pathways.

Janelle Drouin-Ouellet, Shong Lau, Per Ludvik Brattås, Daniella Rylander Ottosson, Karolina Pircs, Daniela A Grassi, Lucy M Collins, Romina Vuono, Annika Andersson Sjöland, Gunilla Westergren-Thorsson and 6 more

Open access · goldAbstract read
In one paragraph

Article in EMBO molecular medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 1 pooled it
4.6field-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

65 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.

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5 more citing papers are in PubMed but not listed here.

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

16 authors at 3 institutions in 2 countries.

Janelle Drouin-OuelletDivision of Neurobiology and Lund Stem Cell Center, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, Lund, Sweden.
Shong LauDivision of Neurobiology and Lund Stem Cell Center, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, Lund, Sweden.
Per Ludvik BrattåsDivision of Neurobiology and Lund Stem Cell Center, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, Lund, Sweden.
Daniella Rylander OttossonDivision of Neurobiology and Lund Stem Cell Center, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, Lund, Sweden.
Karolina PircsDivision of Neurobiology and Lund Stem Cell Center, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, Lund, Sweden.
Daniela A GrassiDivision of Neurobiology and Lund Stem Cell Center, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, Lund, Sweden.
Lucy M CollinsJohn van Geest Centre for Brain Repair & Department of Neurology, Department of Clinical Neurosciences, University of Cambridge, Forvie Site, Cambridge, UK.
Romina VuonoJohn van Geest Centre for Brain Repair & Department of Neurology, Department of Clinical Neurosciences, University of Cambridge, Forvie Site, Cambridge, UK.
Annika Andersson SjölandDepartment of Experimental Medical Science, Unit of Lung Biology BMC, C12 Lund University, Lund, Sweden.
Gunilla Westergren-ThorssonDepartment of Experimental Medical Science, Unit of Lung Biology BMC, C12 Lund University, Lund, Sweden.
Caroline GraffDivision for Neurogeriatrics, Department of NVS, Center for Alzheimer Research, Karolinska Institutet, Huddinge, Sweden.
Lennart MinthonClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
Håkan ToressonClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.
Roger A BarkerDivision of Neurobiology and Lund Stem Cell Center, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, Lund, Sweden.
Johan JakobssonDivision of Neurobiology and Lund Stem Cell Center, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, Lund, Sweden.ORCID 0000-0003-0669-7673
Malin ParmarDivision of Neurobiology and Lund Stem Cell Center, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, Lund, Sweden malin.parmar@med.lu.se.ORCID 0000-0001-5002-4199
Lund University · SEUniversity of Cambridge · GBKarolinska University Hospital · SE

Funding

CIHR 358492Medical Research Council MC_PC_12009
6 · The paper itself

Abstract

Direct conversion of human fibroblasts into mature and functional neurons, termed induced neurons (iNs), was achieved for the first time 6 years ago. This technology offers a promising shortcut for obtaining patient- and disease-specific neurons for disease modeling, drug screening, and other biomedical applications. However, fibroblasts from adult donors do not reprogram as easily as fetal donors, and no current reprogramming approach is sufficiently efficient to allow the use of this technology using patient-derived material for large-scale applications. Here, we investigate the difference in reprogramming requirements between fetal and adult human fibroblasts and identify REST as a major reprogramming barrier in adult fibroblasts. Via functional experiments where we overexpress and knockdown the REST-controlled neuron-specific microRNAs miR-9 and miR-124, we show that the effect of REST inhibition is only partially mediated via microRNA up-regulation. Transcriptional analysis confirmed that REST knockdown activates an overlapping subset of neuronal genes as microRNA overexpression and also a distinct set of neuronal genes that are not activated via microRNA overexpression. Based on this, we developed an optimized one-step method to efficiently reprogram dermal fibroblasts from elderly individuals using a single-vector system and demonstrate that it is possible to obtain iNs of high yield and purity from aged individuals with a range of familial and sporadic neurodegenerative disorders including Parkinson's, Huntington's, as well as Alzheimer's disease.

Indexed as

Cell TransdifferentiationGene Knockdown TechniquesAdultCytological TechniquesFibroblastsGene Expression ProfilingHumansMicroRNAsNeuronsRE1-Silencing Transcription FactorRepressor ProteinsMicroRNAsMIRN124 microRNA, humanMIRN92 microRNA, humanRE1-Silencing Transcription FactorRepressor Proteinsadult human dermal fibroblastsinduced neuronsmicroRNAs 9/9* and 124RE1‐silencing transcription factor

Identifiers

PMID28646119
PMCPMC5538296
OpenAlexW2686521530

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.