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Multi-omic comparison of Alzheimer's variants in human ESC-derived microglia reveals convergence at APOE
Liu T, Zhu B, Liu Y, Zhang X, Yin J, Li X, Jiang L, Hodges AP et al.. The Journal of experimental medicine, 2020-12-01
Topic: Amyloid, tau and blood-test diagnosis
Variations in many genes linked to sporadic Alzheimer's disease (AD) show abundant expression in microglia, but relationships among these genes remain largely elusive. Here, we establish isogenic human ESC-derived microglia-like cell lines (hMGLs) harboring AD variants in CD33, INPP5D, SORL1, and TREM2 loci and curate a comprehensive atlas comprising ATAC-seq, ChIP-seq, RNA-seq, and proteomics datasets. AD-like expression signatures are observed in AD mutant SORL1 and TREM2 hMGLs, while integrative multi-omic analysis of combined epigenetic and expression datasets indicates up-regulation of APOE as a convergent pathogenic node.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Liu, T., Zhu, B., Liu, Y., Zhang, X., Yin, J., Li, X., et al. (2020). Multi-omic comparison of Alzheimer's variants in human ESC-derived microglia reveals convergence at APOE. The Journal of experimental medicine. https://doi.org/10.1084/jem.20200474
Vancouver
Liu T, Zhu B, Liu Y, Zhang X, Yin J, Li X, et al. Multi-omic comparison of Alzheimer's variants in human ESC-derived microglia reveals convergence at APOE. The Journal of experimental medicine. 2020. doi:10.1084/jem.20200474. PMID: 32941599.
BibTeX
@article{liu2020-32941599,
author = {Liu, T. and Zhu, B. and Liu, Y. and Zhang, X. and Yin, J. and Li, X. and Jiang, L. and Hodges, A. P. and others},
title = {{Multi-omic comparison of Alzheimer's variants in human ESC-derived microglia reveals convergence at APOE}},
journal = {The Journal of experimental medicine},
year = {2020},
doi = {10.1084/jem.20200474},
pmid = {32941599},
url = {https://doi.org/10.1084/jem.20200474}
}
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Key findings
- Here, we establish isogenic human ESC-derived microglia-like cell lines (hMGLs) harboring AD variants in CD33, INPP5D, SORL1, and TREM2 loci and curate a comprehensive atlas comprising ATAC-seq, ChIP-seq, RNA-seq, and proteomics datasets.
- AD-like expression signatures are observed in AD mutant SORL1 and TREM2 hMGLs, while integrative multi-omic analysis of combined epigenetic and expression datasets indicates up-regulation of APOE as a convergent pathogenic node.
- We also observe cross-regulatory relationships between SORL1 and TREM2, in which SORL1R744X hMGLs induce TREM2 expression to enhance APOE expression.
- AD-associated SORL1 and TREM2 mutations also impaired hMGL Aβ uptake in an APOE-dependent manner in vitro and attenuated Aβ uptake/clearance in mouse AD brain xenotransplants.
Why it matters
Using human embryonic stem cell-derived microglia-like cells carrying Alzheimer's-linked variants in CD33, INPP5D, SORL1 and TREM2, the study found Alzheimer's-like expression signatures in SORL1 and TREM2 cells and up-regulation of APOE as a convergent node. This is a cell-based laboratory study, not a treatment in people, so it does not show how to treat, cure or prevent Alzheimer's.
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Study details
- Evidence strengthLow
How this study scored 50/100
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 (The Journal of experimental medicine) |
| Journal's citation record | 4 / 4 | The Journal of Experimental Medicine: journal h-index 652 (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 | 2020 — 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 | 4 / 7 | Cited 70 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.8 citations a year over 8 year(s) since 2020 |
| Impact for its field and year | 3 / 6 | Cited 4.9× 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 31 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Huaxi Xu: h-index 85 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 32941599) |
| Free to read | 2 / 2 | Free to read |
| Total | 50 / 100 | — |
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Read the original
- DOI: 10.1084/jem.20200474
- PubMed: 32941599
- Original source →
- Free full text: The Journal of Experimental Medicine →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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