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Functional Studies of Missense TREM2 Mutations in Human Stem Cell-Derived Microglia
Brownjohn PW, Smith J, Solanki R, Lohmann E, Houlden H, Hardy J, Dietmann S, Livesey FJ.. Stem cell reports, 2018-03-29
Topic: Brain proteins, microglia and lab models
The derivation of microglia from human stem cells provides systems for understanding microglial biology and enables functional studies of disease-causing mutations. We describe a robust method for the derivation of human microglia from stem cells, which are phenotypically and functionally comparable with primary microglia. We used stem cell-derived microglia to study the consequences of missense mutations in the microglial-expressed protein triggering receptor expressed on myeloid cells 2 (TREM2), which are causal for frontotemporal dementia-like syndrome and Nasu-Hakola disease.
Key findings
- We describe a robust method for the derivation of human microglia from stem cells, which are phenotypically and functionally comparable with primary microglia.
- We used stem cell-derived microglia to study the consequences of missense mutations in the microglial-expressed protein triggering receptor expressed on myeloid cells 2 (TREM2), which are causal for frontotemporal dementia-like syndrome and Nasu-Hakola disease.
- We find that mutant TREM2 accumulates in its immature form, does not undergo typical proteolysis, and is not trafficked to the plasma membrane.
- However, in the absence of plasma membrane TREM2, microglia differentiate normally, respond to stimulation with lipopolysaccharide, and are phagocytically competent.
Why it matters
Using microglia grown from human stem cells, this study found that TREM2 mutations causing frontotemporal dementia-like syndrome and Nasu-Hakola disease produce an immature TREM2 protein that does not mature properly. It is laboratory cell work on rare genetic diseases and does not show a treatment, cure or prevention for Alzheimer's.
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Study details
- Evidence strengthLow
How this study scored 47/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Stem cell reports) |
| Journal's citation record | 1 / 4 | Stem Cell Reports: journal h-index 146 (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 | 2 / 5 | 2018 — within 10 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 | 5 / 7 | Cited 193 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 19.3 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 3 / 6 | Cited 6.0× 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 | 3 / 4 | Cited 65 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Frederick J. Livesey: h-index 49 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29606617) |
| Free to read | 2 / 2 | Free to read |
| Total | 47 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.stemcr.2018.03.003
- PubMed: 29606617
- Original source →
- Free full text: Stem Cell Reports →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Brownjohn, P. W., Smith, J., Solanki, R., Lohmann, E., Houlden, H., Hardy, J., et al. (2018). Functional Studies of Missense TREM2 Mutations in Human Stem Cell-Derived Microglia. Stem cell reports. https://doi.org/10.1016/j.stemcr.2018.03.003
Vancouver
Brownjohn PW, Smith J, Solanki R, Lohmann E, Houlden H, Hardy J, et al. Functional Studies of Missense TREM2 Mutations in Human Stem Cell-Derived Microglia. Stem cell reports. 2018. doi:10.1016/j.stemcr.2018.03.003. PMID: 29606617.
BibTeX
@article{brownjohn2018-29606617,
author = {Brownjohn, P. W. and Smith, J. and Solanki, R. and Lohmann, E. and Houlden, H. and Hardy, J. and Dietmann, S. and Livesey, F. J.},
title = {{Functional Studies of Missense TREM2 Mutations in Human Stem Cell-Derived Microglia}},
journal = {Stem cell reports},
year = {2018},
doi = {10.1016/j.stemcr.2018.03.003},
pmid = {29606617},
url = {https://doi.org/10.1016/j.stemcr.2018.03.003}
}
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