Evidence map›Paper›PMID 32184029›Full record

ArticleNeurobiology of aging2020

A three-dimensional dementia model reveals spontaneous cell cycle re-entry and a senescence-associated secretory phenotype.

Veronica Porterfield, Shahzad S Khan, Erin P Foff, Mehmet Murat Koseoglu, Isabella K Blanco, Sruthi Jayaraman, Eric Lien, Michael J McConnell, George S Bloom, John S Lazo and 1 more

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

Article in Neurobiology of aging, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.9field-weighted citation impact, top 22% 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

9 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. METTL3-mediated mTranslational psychiatry · 2026
    Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. CSF IL-8 Associated with Response to Gene Therapy in a Case Series of Spinal Muscular Atrophy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023
    Article
  8. Review
  9. 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

11 authors at 1 institution in 1 country.

Veronica PorterfieldDepartment of Neurology, University of Virginia, Charlottesville, VA, USA; University of Virginia Stem Cell Core, Office of Research Core Administration, University of Virginia, Charlottesville, VA, USA; Department of Cell Biology, University of Virginia, Charlottesville, VA, USA.
Shahzad S KhanDepartment of Biology, University of Virginia, Charlottesville, VA, USA.
Erin P FoffDepartment of Neurology, University of Virginia, Charlottesville, VA, USA.
Mehmet Murat KoseogluDepartment of Biology, University of Virginia, Charlottesville, VA, USA; Department of Pharmacology, University of Virginia, Charlottesville, VA, USA; Fiske Drug Discovery Laboratory, University of Virginia, Charlottesville, VA, USA.
Isabella K BlancoDepartment of Pharmacology, University of Virginia, Charlottesville, VA, USA.
Sruthi JayaramanDepartment of Pharmacology, University of Virginia, Charlottesville, VA, USA.
Eric LienDepartment of Pharmacology, University of Virginia, Charlottesville, VA, USA.
Michael J McConnellDepartment of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, USA; Department of Neuroscience, University of Virginia, Charlottesville, VA, USA.
George S BloomDepartment of Cell Biology, University of Virginia, Charlottesville, VA, USA; Department of Biology, University of Virginia, Charlottesville, VA, USA; Department of Neuroscience, University of Virginia, Charlottesville, VA, USA.
John S LazoDepartment of Pharmacology, University of Virginia, Charlottesville, VA, USA; Fiske Drug Discovery Laboratory, University of Virginia, Charlottesville, VA, USA.
Elizabeth R SharlowDepartment of Pharmacology, University of Virginia, Charlottesville, VA, USA; Fiske Drug Discovery Laboratory, University of Virginia, Charlottesville, VA, USA. Electronic address: ers7g@virginia.edu.
University of Virginia · US

Funding

Linking Tau Structure to Its Functions and Mechanisms in Alzheimer’s DiseaseRF1AG051085 · NIA · UNIVERSITY OF VIRGINIA · PI BLOOM, GEORGE S · 2016 to 2016
$1.8M
A Precision high content screening assay for AB-mediated neuronal cell cycle reentryR01AG063400 · NIA · UNIVERSITY OF VIRGINIA · PI SHARLOW, ELIZABETH · 2019 to 2021
$1.4M
NIA NIH HHS R01 AG063400NIA NIH HHS RF1 AG051085
6 · The paper itself

Abstract

A hexanucleotide repeat expansion on chromosome 9 open reading frame 72 (C9orf72) is associated with familial amyotrophic lateral sclerosis (ALS) and a subpopulation of patients with sporadic ALS and frontotemporal dementia. We used inducible pluripotent stem cells from neurotypic and C9orf72+ (C9+) ALS patients to derive neuronal progenitor cells. We demonstrated that C9+ and neurotypic neuronal progenitor cells differentiate into neurons. The C9+ neurons, however, spontaneously re-expressed cyclin D1 after 12 weeks, suggesting cell cycle re-engagement. Gene profiling revealed significant increases in senescence-associated genes in C9+ neurons. Moreover, C9+ neurons expressed high levels of mRNA for CXCL8, a chemokine overexpressed by senescent cells, while media from C9+ neurons contained significant levels of CXCL8, CXCL1, IL13, IP10, CX3CL1, and reactive oxygen species, which are components of the senescence-associated secretory phenotype. Thus, re-engagement of cell cycle-associated proteins and a senescence-associated secretory phenotype could be fundamental components of neuronal dysfunction in ALS and frontotemporal dementia.

Indexed as

DNA Repeat ExpansionAmyotrophic Lateral SclerosisC9orf72 ProteinCell CycleCells, CulturedCellular SenescenceFrontotemporal DementiaGene ExpressionGene Expression Regulation, DevelopmentalHumansInduced Pluripotent Stem CellsInterleukin-8RNA, MessengerStem CellsC9orf72 ProteinC9orf72 protein, humanCXCL8 protein, humanInterleukin-8RNA, MessengerAmyotrophic lateral sclerosisCell cycle re-entryFrontotemporal dementiaSenescenceSenescence-associated secretory phenotype

Identifiers

PMID32184029
PMCPMC7166179
OpenAlexW3007016818

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.