Evidence map›Paper›PMID 41307999›Full record

ArticleCell reports2025

Spatial and single-cell transcriptomics reveal the reorganization of cerebellar microglia with aging.

Andy P Tsai, Douglas E Henze, Eduardo Ramirez Lopez, James Haberberger, Chuanpeng Dong, Nannan Lu, Micaiah Atkins, Emma K Costa, Amelia Farinas, Hamilton Se-Hwee Oh and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
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

8 citing papers in PubMed.

  1. Review
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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

15 authors.

Andy P TsaiDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA; Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.
Douglas E HenzeDepartment of Bioengineering, Stanford University, Stanford, CA, USA.
Eduardo Ramirez LopezDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA; Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.
James HaberbergerThe Phil and Penny Knight Initiative for Brain Resilience, Stanford University, Stanford, CA, USA.
Chuanpeng DongDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Nannan LuDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA; Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.
Micaiah AtkinsDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA; Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA; State University of New York Downstate Health Science University, College of Medicine, Brooklyn, NY, USA.
Emma K CostaDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA; Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA; Neurosciences Interdepartmental Program, Stanford University School of Medicine, Stanford, CA, USA.
Amelia FarinasDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA; Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA; Neurosciences Interdepartmental Program, Stanford University School of Medicine, Stanford, CA, USA.
Hamilton Se-Hwee OhDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA; Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.
Patricia Moran-LosadaDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA; Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.
Yann Le GuenQuantitative Sciences Unit, Department of Medicine, Stanford University, Stanford, CA, USA.
Alina IsakovaThe Phil and Penny Knight Initiative for Brain Resilience, Stanford University, Stanford, CA, USA.
Stephen R QuakeDepartment of Bioengineering, Stanford University, Stanford, CA, USA; Department of Applied Physics, Stanford University, Stanford, CA, USA; Chan Zuckerberg Initiative, Redwood City, CA, USA. Electronic address: steve@quake-lab.org.
Tony Wyss-CorayDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA; Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA; The Phil and Penny Knight Initiative for Brain Resilience, Stanford University, Stanford, CA, USA. Electronic address: twc@stanford.edu.

Funding

Molecular signature of parabiosisR01AG072255 · NIA · STANFORD UNIVERSITY · PI WYSS-CORAY, TONY · 2021 to 2025
$2.4M
NIA NIH HHS R01 AG072255
6 · The paper itself

Abstract

The cerebellum, essential for motor coordination and increasingly recognized for its role in cognition, is typically considered more resilient to aging and largely spared from hallmark Alzheimer's disease (AD) pathology. However, transcriptomic analyses across fifteen mouse brain regions revealed that the cerebellum undergoes some of the earliest and most pronounced age-related changes. To investigate cerebellar aging, we applied single-nucleus RNA sequencing (RNA-seq), microglial bulk RNA-seq, and multiplexed error-robust fluorescence in situ hybridization (MERFISH)-based spatial transcriptomics. Microglia showed the most prominent changes, including elevated expression of a neuroprotective signature and reduced expression of a lipid-droplet-accumulating signature compared to hippocampal microglia. Spatial analyses further revealed that aged cerebellar microglia were positioned in close proximity to granule cells. Utilizing this relationship, we identified a proximity-dependent transcriptional state defined by the neuron-associated microglial signature. This signature reveals a region-specific microglial adaptation, highlighting cerebellar reorganization with age and potential resilience to AD.

Indexed as

AgingCerebellumMicrogliaSingle-Cell AnalysisTranscriptomeAnimalsGene Expression ProfilingHippocampusMaleMiceMice, Inbred C57BLbrain agingcerebellumCP: neurosciencedisease susceptibilityhippocampuslipid-droplet-accumulating microgliamulti-omicsneuron-associated microglianeuroprotective microgliaregion- and age-specific transcriptional profilesspatial transcriptomics

Identifiers

PMID41307999
PMCPMC12904544

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.