Evidence map›Paper›PMID 33567283›Full record

ArticleCell reports2021

Natural genetic variation determines microglia heterogeneity in wild-derived mouse models of Alzheimer's disease.

Hongtian Stanley Yang, Kristen D Onos, Kwangbom Choi, Kelly J Keezer, Daniel A Skelly, Gregory W Carter, Gareth R Howell

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed, 1 pooled it
5.6field-weighted citation impact, top 3% 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

50 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Modern Mining: The Role of Single-cell RNA Sequencing in Advancing Neuroscience Research.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026
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  5. IL1A enhances TNF-induced retinal ganglion cell death.Frontiers in aging neuroscience · 2026
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  8. WSB.bioRxiv : the preprint server for biology · 2025
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  10. Review
  11. Acute Communication Between Microglia and Nonparenchymal Immune Cells in the Anti-Aβ Antibody-Injected Cortex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Genetic diversity promotes resilience in a mouse model of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    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 2 institutions in 1 country.

Hongtian Stanley YangThe Jackson Laboratory, Bar Harbor, ME 04609, USA.
Kristen D OnosThe Jackson Laboratory, Bar Harbor, ME 04609, USA.
Kwangbom ChoiThe Jackson Laboratory, Bar Harbor, ME 04609, USA.
Kelly J KeezerThe Jackson Laboratory, Bar Harbor, ME 04609, USA.
Daniel A SkellyThe Jackson Laboratory, Bar Harbor, ME 04609, USA.
Gregory W CarterThe Jackson Laboratory, Bar Harbor, ME 04609, USA; Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111, USA; Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, ME 04469, USA.
Gareth R HowellThe Jackson Laboratory, Bar Harbor, ME 04609, USA; Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111, USA; Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, ME 04469, USA. Electronic address: gareth.howell@jax.org.
Jackson Laboratory · USTufts University · US

Funding

TREAT AD Structural Biology CoreU54AG065187 · NIA · EMORY UNIVERSITY · PI ALLAN I LEVEY · 2019 to 2026
$69.7M
Systems Genetics Approach to Determine Interactors of Apolipoprotein E in Alzheimer’s DiseaseRF1AG055104 · NIA · JACKSON LABORATORY · PI CARTER, GREGORY W, HOWELL, GARETH R · 2018 to 2018
$4.1M
Investigating the Role of Complement-expressing Myeloid Cells in Synapse Loss and Vascular Compromise in Alzheimers DiseaseRF1AG051496 · NIA · JACKSON LABORATORY · PI HOWELL, GARETH R, STEVENS, BETH ANN · 2015 to 2018
$3.7M
NIA NIH HHS RF1 AG051496NIA NIH HHS RF1 AG055104NIA NIH HHS U54 AG065187
6 · The paper itself

Abstract

Genetic and genome-wide association studies suggest a central role for microglia in Alzheimer's disease (AD). However, single-cell RNA sequencing (scRNA-seq) of microglia in mice, a key preclinical model, has shown mixed results regarding translatability to human studies. To address this, scRNA-seq of microglia from C57BL/6J (B6) and wild-derived strains (WSB/EiJ, CAST/EiJ, and PWK/PhJ) with and without APP/PS1 demonstrates that genetic diversity significantly alters features and dynamics of microglia in baseline neuroimmune functions and in response to amyloidosis. Results show significant variation in the abundance of microglial subtypes or states, including numbers of previously identified disease-associated and interferon-responding microglia, across the strains. For each subtype, significant differences in the expression of many genes are observed in wild-derived strains relative to B6, including 19 genes previously associated with human AD including Apoe, Trem2, and Sorl1. This resource is critical in the development of appropriately targeted therapeutics for AD and other neurological diseases.

Indexed as

RNA-SeqAlzheimer DiseaseAnimalsDisease Models, AnimalGenetic VariationGenome-Wide Association StudyMiceMicrogliaSpecies SpecificityADAlzheimer's diseaseAPP/PS1CAST/EiJDAMdisease-associated microgliagenetic diversityinterferon-responding microgliaIRMmicrogliaPWK/PhJwild-derivedWSB/EiJ

Identifiers

PMID33567283
PMCPMC7937391
OpenAlexW3128058731

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.