Evidence map›Paper›PMID 28618077›Full record

ArticleGlia2017

Generation of a microglial developmental index in mice and in humans reveals a sex difference in maturation and immune reactivity.

Richa Hanamsagar, Mark D Alter, Carina S Block, Haley Sullivan, Jessica L Bolton, Staci D Bilbo

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Glia, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 238 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
238citing papers in PubMed, 3 pooled it
17.2field-weighted citation impact, top 1% 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

238 citing papers in PubMed, 3 syntheses or guidelines pooled it, 400 citations in OpenAlex.

  1. Pooled it
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  10. Increased circulating TREM2Brain, behavior, & immunity - health · 2026
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178 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Richa HanamsagarDepartment of Pediatrics, Lurie Center for Autism, Massachusetts General Hospital for Children, Harvard Medical School, Boston, Massachusetts, 02129.ORCID 0000-0003-3227-5132
Mark D AlterDepartment of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, 19104.
Carina S BlockDepartment of Psychology and Neuroscience, Duke University, Durham, North Carolina, 27708.
Haley SullivanDepartment of Psychology and Neuroscience, Duke University, Durham, North Carolina, 27708.
Jessica L BoltonDepartment of Psychology and Neuroscience, Duke University, Durham, North Carolina, 27708.
Staci D BilboDepartment of Pediatrics, Lurie Center for Autism, Massachusetts General Hospital for Children, Harvard Medical School, Boston, Massachusetts, 02129.
Duke University · USHarvard University · USUniversity of Pennsylvania · US

Funding

Sex Differences in Developing Microglia: Implications for Synaptic PruningR01MH101183 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI BILBO, STACI D · 2013 to 2017
$2.0M
NIMH NIH HHS R01 MH101183
6 · The paper itself

Abstract

Evidence suggests many neurological disorders emerge when normal neurodevelopmental trajectories are disrupted, i.e., when circuits or cells do not reach their fully mature state. Microglia play a critical role in normal neurodevelopment and are hypothesized to contribute to brain disease. We used whole transcriptome profiling with Next Generation sequencing of purified developing microglia to identify a microglial developmental gene expression program involving thousands of genes whose expression levels change monotonically (up or down) across development. Importantly, the gene expression program was delayed in males relative to females and exposure of adult male mice to LPS, a potent immune activator, accelerated microglial development in males. Next, a microglial developmental index (MDI) generated from gene expression patterns obtained from purified mouse microglia, was applied to human brain transcriptome datasets to test the hypothesis that variability in microglial development is associated with human diseases such as Alzheimer's and autism where microglia have been suggested to play a role. MDI was significantly increased in both Alzheimer's Disease and in autism, suggesting that accelerated microglial development may contribute to neuropathology. In conclusion, we identified a microglia-specific gene expression program in mice that was used to create a microglia developmental index, which was applied to human datasets containing heterogeneous cell types to reveal differences between healthy and diseased brain samples, and between males and females. This powerful tool has wide ranging applicability to examine microglial development within the context of disease and in response to other variables such as stress and pharmacological treatments.

Indexed as

Gene Expression ProfilingGene Expression Regulation, DevelopmentalSex CharacteristicsAnimalsCells, CulturedEscherichia coliEstrous CycleFemaleHippocampusHumansLipopolysaccharidesMaleMiceMice, Inbred C57BLMicrogliaNeuroimmunomodulationLipopolysaccharidesdevelopmentmicrogliasex differenceswhole transcriptome analysis

Identifiers

PMID28618077
PMCPMC5540146
OpenAlexW2977622316

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.