Evidence map›Paper›PMID 32647121›Full record

ArticleScientific reports2020

Transcriptional repression of PTEN in neural cells using CRISPR/dCas9 epigenetic editing.

C Moses, S I Hodgetts, F Nugent, G Ben-Ary, K K Park, P Blancafort, A R Harvey

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.0field-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

13 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. From Bench to Bed: The Current Genome Editing Therapies for Glaucoma.Frontiers in cell and developmental biology · 2022
    Review
  11. Review
  12. Article
  13. 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

7 authors at 4 institutions in 2 countries.

C MosesSchool of Human Sciences, Faculty of Science, The University of Western Australia, 35 Stirling Highway, Perth, WA, 6009, Australia.
S I HodgettsSchool of Human Sciences, Faculty of Science, The University of Western Australia, 35 Stirling Highway, Perth, WA, 6009, Australia.
F NugentCancer Epigenetics Laboratory, The Harry Perkins Institute of Medical Research, 6 Verdun Street, Nedlands, WA, 6009, Australia.
G Ben-ArySchool of Human Sciences, Faculty of Science, The University of Western Australia, 35 Stirling Highway, Perth, WA, 6009, Australia.
K K ParkDepartment of Neurological Surgery, Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
P BlancafortSchool of Human Sciences, Faculty of Science, The University of Western Australia, 35 Stirling Highway, Perth, WA, 6009, Australia. pilar.blancafort@uwa.edu.au.
A R HarveySchool of Human Sciences, Faculty of Science, The University of Western Australia, 35 Stirling Highway, Perth, WA, 6009, Australia. alan.harvey@uwa.edu.au.
University of Western Australia · AUHarry Perkins Institute of Medical Research · AUNeurological Surgery · USPerron Institute for Neurological and Translational Science · AU

Funding

Targeted epigenetic silencing of oncogenic Transcription Factors (PQ18)R01CA170370 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BLANCAFORT, PILAR · 2012 to 2015
$900k
Precision engineering of DNA methylation patterns in the human genomeR01DA036906 · NIDA · UNIVERSITY OF WESTERN AUSTRALIA · PI BLANCAFORT, PILAR, LISTER, RYAN · 2013 to 2014
$350k
NCI NIH HHS R01 CA170370NIDA NIH HHS R01 DA036906NIH HHS R01CA170370NIH HHS R01DA036906
6 · The paper itself

Abstract

After damage to the adult mammalian central nervous system (CNS), surviving neurons have limited capacity to regenerate and restore functional connectivity. Conditional genetic deletion of PTEN results in robust CNS axon regrowth, while PTEN repression with short hairpin RNA (shRNA) improves regeneration but to a lesser extent, likely due to suboptimal PTEN mRNA knockdown using this approach. Here we employed the CRISPR/dCas9 system to repress PTEN transcription in neural cells. We targeted the PTEN proximal promoter and 5' untranslated region with dCas9 fused to the repressor protein Krüppel-associated box (KRAB). dCas9-KRAB delivered in a lentiviral vector with one CRISPR guide RNA (gRNA) achieved potent and specific PTEN repression in human cell line models and neural cells derived from human iPSCs, and induced histone (H)3 methylation and deacetylation at the PTEN promoter. The dCas9-KRAB system outperformed a combination of four shRNAs targeting the PTEN transcript, a construct previously used in CNS injury models. The CRISPR system also worked more effectively than shRNAs for Pten repression in rat neural crest-derived PC-12 cells, and enhanced neurite outgrowth after nerve growth factor stimulation. PTEN silencing with CRISPR/dCas9 epigenetic editing may provide a new option for promoting axon regeneration and functional recovery after CNS trauma.

Indexed as

5' Untranslated RegionsAnimalsAxonsCell Line, TumorCRISPR-Cas SystemsGene EditingGenetic TherapyGenetic VectorsHEK293 CellsHumansLentivirusNerve RegenerationNeuronal OutgrowthOptic NerveOptic Nerve InjuriesPromoter Regions, Genetic5' Untranslated RegionsPTEN PhosphohydrolasePTEN protein, humanPten protein, ratRepressor ProteinsRNA, Guide, CRISPR-Cas SystemsRNA, Small Interfering

Identifiers

PMID32647121
PMCPMC7347541
OpenAlexW3041664957

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.