Transcriptional signature in microglia associated with Aβ plaque phagocytosis
Grubman A, Choo XY, Chew G, Ouyang JF, Sun G, Croft NP, Rossello FJ, Simmons R et al.. Nature communications, 2021-05-21
Topic: Inflammation, microglia and astrocytes
The role of microglia cells in Alzheimer's disease (AD) is well recognized, however their molecular and functional diversity remain unclear. Here, we isolated amyloid plaque-containing (using labelling with methoxy-XO4, XO4 + ) and non-containing (XO4 - ) microglia from an AD mouse model. Transcriptomics analysis identified different transcriptional trajectories in ageing and AD mice. XO4 + microglial transcriptomes demonstrated dysregulated expression of genes associated with late onset AD. We further showed that the transcriptional program associated with XO4 + microglia from mice is present in a subset of human microglia isolated from brains of individuals with AD. XO4 - microglia displayed transcriptional signatures associated with accelerated ageing and contained more intracellular post-synaptic material than XO4 + microglia, despite reduced active synaptosome phagocytosis. We identified HIF1α as potentially regulating synaptosome phagocytosis in vitro using primary human microglia, and BV2 mouse microglial cells. Together, these findings provide insight into molecular mechanisms underpinning the functional diversity of microglia in AD.
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APA 7th
Grubman, A., Choo, X. Y., Chew, G., Ouyang, J. F., Sun, G., Croft, N. P., et al. (2021). Transcriptional signature in microglia associated with Aβ plaque phagocytosis. Nature communications. https://doi.org/10.1038/s41467-021-23111-1
Vancouver
Grubman A, Choo XY, Chew G, Ouyang JF, Sun G, Croft NP, et al. Transcriptional signature in microglia associated with Aβ plaque phagocytosis. Nature communications. 2021. doi:10.1038/s41467-021-23111-1. PMID: 34021136.
BibTeX
@article{grubman2021-34021136,
author = {Grubman, A. and Choo, X. Y. and Chew, G. and Ouyang, J. F. and Sun, G. and Croft, N. P. and Rossello, F. J. and Simmons, R. and others},
title = {{Transcriptional signature in microglia associated with Aβ plaque phagocytosis}},
journal = {Nature communications},
year = {2021},
doi = {10.1038/s41467-021-23111-1},
pmid = {34021136},
url = {https://doi.org/10.1038/s41467-021-23111-1}
}
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Key findings
- XO4 + microglial transcriptomes demonstrated dysregulated expression of genes associated with late onset AD.
- We further showed that the transcriptional program associated with XO4 + microglia from mice is present in a subset of human microglia isolated from brains of individuals with AD.
- XO4 - microglia displayed transcriptional signatures associated with accelerated ageing and contained more intracellular post-synaptic material than XO4 + microglia, despite reduced active synaptosome phagocytosis.
- Together, these findings provide insight into molecular mechanisms underpinning the functional diversity of microglia in AD.
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Study details
- Evidence strengthLow
How this study scored 47/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 27 of the 58 points we could judge it on, which is 47 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature communications) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34021136) |
| Free to read | 2 / 2 | Free to read |
| Points | 27 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 27 of the 58 points we could judge it on is 47 out of 100. |
| Total | 47 / 100 | — |
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