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TREM2 regulates purinergic receptor-mediated calcium signaling and motility in human iPSC-derived microglia
Jairaman A, McQuade A, Granzotto A, Kang YJ, Chadarevian JP, Gandhi S, Parker I, Smith I et al.. eLife, 2022-02-22
Topic: Brain proteins, microglia and lab models
The membrane protein TREM2 (Triggering Receptor Expressed on Myeloid cells 2) regulates key microglial functions including phagocytosis and chemotaxis. Loss-of-function variants of TREM2 are associated with increased risk of Alzheimer's disease (AD). Because abnormalities in Ca 2+ signaling have been observed in several AD models, we investigated TREM2 regulation of Ca 2+ signaling in human induced pluripotent stem cell-derived microglia (iPSC-microglia) with genetic deletion of TREM2.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Jairaman, A., McQuade, A., Granzotto, A., Kang, Y. J., Chadarevian, J. P., Gandhi, S., et al. (2022). TREM2 regulates purinergic receptor-mediated calcium signaling and motility in human iPSC-derived microglia. eLife. https://doi.org/10.7554/elife.73021
Vancouver
Jairaman A, McQuade A, Granzotto A, Kang YJ, Chadarevian JP, Gandhi S, et al. TREM2 regulates purinergic receptor-mediated calcium signaling and motility in human iPSC-derived microglia. eLife. 2022. doi:10.7554/elife.73021. PMID: 35191835.
BibTeX
@article{jairaman2022-35191835,
author = {Jairaman, A. and McQuade, A. and Granzotto, A. and Kang, Y. J. and Chadarevian, J. P. and Gandhi, S. and Parker, I. and Smith, I. and others},
title = {{TREM2 regulates purinergic receptor-mediated calcium signaling and motility in human iPSC-derived microglia}},
journal = {eLife},
year = {2022},
doi = {10.7554/elife.73021},
pmid = {35191835},
url = {https://doi.org/10.7554/elife.73021}
}
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Key findings
- Loss-of-function variants of TREM2 are associated with increased risk of Alzheimer's disease (AD).
- Because abnormalities in Ca 2+ signaling have been observed in several AD models, we investigated TREM2 regulation of Ca 2+ signaling in human induced pluripotent stem cell-derived microglia (iPSC-microglia) with genetic deletion of TREM2.
- We found that iPSC-microglia lacking TREM2 (TREM2 KO) show exaggerated Ca 2+ signals in response to purinergic agonists, such as ADP, that shape microglial injury responses.
- This ADP hypersensitivity, driven by increased expression of P2Y 12 and P2Y 13 receptors, results in greater release of Ca 2+ from the endoplasmic reticulum stores, which triggers sustained Ca 2+ influx through Orai channels and alters cell motility in TREM2 KO microglia.
Why it matters
In human iPSC-derived microglia, deleting TREM2 caused exaggerated calcium signals in response to purinergic agonists. This is cell-based research, so it is early and does not yet show a treatment for people.
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Study details
- Evidence strengthLow
How this study scored 49/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported and randomized / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 47 of the 96 points we could judge it on, which is 49 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (eLife) |
| Journal's citation record | 3 / 4 | ELife: journal h-index 311 (OpenAlex, 2026-10-29) |
| 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 | 2022 — 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 | Laboratory or animal study (title names “ipsc”) — scores zero |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 63 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 10.5 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 3 / 6 | Cited 3.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 2 / 4 | Cited 34 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 1 / 3 | University of California, Irvine: institution h-index 1,195 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 35191835) |
| Free to read | 2 / 2 | Free to read |
| Points | 47 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 47 of the 96 points we could judge it on is 49 out of 100. |
| Total | 49 / 100 | — |
What each of these 20 components measures, and what this score is not →
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