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Type-I-interferon signaling drives microglial dysfunction and senescence in human iPSC models of Down syndrome and Alzheimer's disease
Jin M, Xu R, Wang L, Alam MM, Ma Z, Zhu S, Martini AC, Jadali A et al.. Cell stem cell, 2022-07-01
Topic: Inflammation, microglia and astrocytes
Microglia are critical in brain development and Alzheimer's disease (AD) etiology. Down syndrome (DS) is the most common genetic developmental disorder and risk factor for AD. Surprisingly, little information is available on the impact of trisomy of human chromosome 21 (Hsa21) on microglial functions during DS brain development and in AD in DS. Using induced pluripotent stem cell (iPSC)-based organoid and chimeric mouse models, we report that DS microglia exhibit an enhanced synaptic pruning function, which alters neuronal synaptic functions. In response to human brain tissue-derived pathological tau, DS microglia undergo cellular senescence and exhibit elevated type-I-interferon signaling. Mechanistically, knockdown of Hsa21-encoded type I interferon receptors, IFNARs, rescues the DS microglial phenotypes both during brain development and in response to pathological tau. Our findings provide in vivo evidence that human microglia respond to pathological tau by exhibiting dystrophic phenotypes. Targeting IFNARs may improve DS microglial functions and prevent senescence.
Key findings
- Our findings provide in vivo evidence that human microglia respond to pathological tau by exhibiting dystrophic phenotypes.
Study details
- Evidence strengthLow
How this study scored 40/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported 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 23 of the 58 points we could judge it on, which is 40 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Cell stem cell) |
| 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 | 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 |
| 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 35803230) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 23 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 23 of the 58 points we could judge it on is 40 out of 100. |
| Total | 40 / 100 | — |
What each of these 20 components measures, and what this score is not →
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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APA 7th
Jin, M., Xu, R., Wang, L., Alam, M. M., Ma, Z., Zhu, S., et al. (2022). Type-I-interferon signaling drives microglial dysfunction and senescence in human iPSC models of Down syndrome and Alzheimer's disease. Cell stem cell. https://doi.org/10.1016/j.stem.2022.06.007
Vancouver
Jin M, Xu R, Wang L, Alam MM, Ma Z, Zhu S, et al. Type-I-interferon signaling drives microglial dysfunction and senescence in human iPSC models of Down syndrome and Alzheimer's disease. Cell stem cell. 2022. doi:10.1016/j.stem.2022.06.007. PMID: 35803230.
BibTeX
@article{jin2022-35803230,
author = {Jin, M. and Xu, R. and Wang, L. and Alam, M. M. and Ma, Z. and Zhu, S. and Martini, A. C. and Jadali, A. and others},
title = {{Type-I-interferon signaling drives microglial dysfunction and senescence in human iPSC models of Down syndrome and Alzheimer's disease}},
journal = {Cell stem cell},
year = {2022},
doi = {10.1016/j.stem.2022.06.007},
pmid = {35803230},
url = {https://doi.org/10.1016/j.stem.2022.06.007}
}
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