Evidence map›Paper›PMID 34294785›Full record

ArticleScientific reports2021

Modest changes in Spi1 dosage reveal the potential for altered microglial function as seen in Alzheimer's disease.

Ruth E Jones, Robert Andrews, Peter Holmans, Matthew Hill, Philip R Taylor

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 24 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 2 pooled it
4.1field-weighted citation impact, top 5% 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

24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 40 citations in OpenAlex.

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  18. Alzheimer's Disease: An Updated Overview of Its Genetics.International journal of molecular sciences · 2023
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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.

Ruth E JonesDivision of Infection and Immunity, Cardiff University, Cardiff, UK.
Robert AndrewsDivision of Infection and Immunity, Cardiff University, Cardiff, UK.
Peter HolmansDivision of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
Matthew HillUK Dementia Research Institute at Cardiff, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff, CF24 4HQ, UK.
Philip R TaylorDivision of Infection and Immunity, Cardiff University, Cardiff, UK. TaylorPR@cardiff.ac.uk.
Cardiff University · GBUK Dementia Research Institute · GB

Funding

Medical Research Council MR/L010305/1Wellcome TrustWellcome Trust 107964/Z/15/Z
6 · The paper itself

Abstract

Genetic association studies have identified multiple variants at the SPI1 locus that modify risk and age of onset for Alzheimer's Disease (AD). Reports linking risk variants to gene expression suggest that variants denoting higher SPI1 expression are likely to have an earlier AD onset, and several other AD risk genes contain PU.1 binding sites in the promoter region. Overall, this suggests the level of SPI1 may alter microglial phenotype potentially impacting AD. This study determined how the microglial transcriptome was altered following modest changes to Spi1 expression in primary mouse microglia. RNA-sequencing was performed on microglia with reduced or increased Spi1/PU.1 expression to provide an unbiased approach to determine transcriptomic changes affected by Spi1. In summary, a reduction in microglial Spi1 resulted in the dysregulation of transcripts encoding proteins involved in DNA replication pathways while an increased Spi1 results in an upregulation of genes associated with immune response pathways. Additionally, a subset of 194 Spi1 dose-sensitive genes was identified and pathway analysis suggests that several innate immune and interferon response pathways are impacted by the concentration of Spi1. Together these results suggest Spi1 levels can alter the microglial transcriptome and suggests interferon pathways may be altered in individuals with AD related Spi1 risk SNPs.

Indexed as

Gene DosageGene Regulatory NetworksAlzheimer DiseaseAnimalsGene Expression ProfilingHumansInterferonsMiceMicrogliaPolymorphism, Single NucleotidePrimary Cell CultureProto-Oncogene ProteinsProto-Oncogene Protein Spi-1Sequence Analysis, RNASignal TransductionTrans-ActivatorsInterferonsProto-Oncogene ProteinsProto-Oncogene Protein Spi-1Trans-Activators

Identifiers

PMID34294785
PMCPMC8298495
OpenAlexW3133041819

What OpenQuestion holds

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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.