Profiling senescent cells in human brains reveals neurons with CDKN2D/p19 and tau neuropathology
Dehkordi SK, Walker J, Sah E, Bennett E, Atrian F, Frost B, Woost B, Bennett RE et al.. Nature aging, 2021-12-10
Topic: Brain proteins, microglia and lab models
Senescent cells contribute to pathology and dysfunction in animal models 1 . Their sparse distribution and heterogenous phenotype have presented challenges for detecting them in human tissues. We developed a senescence eigengene approach to identify these rare cells within large, diverse populations of postmortem human brain cells. Eigengenes are useful when no single gene reliably captures a phenotype, like senescence; they also help to reduce noise, which is important in large transcriptomic datasets where subtle signals from low-expressing genes can be lost. Each of our eigengenes detected ~2% senescent cells from a population of ~140,000 single nuclei derived from 76 postmortem human brains with various levels of Alzheimer's disease (AD) pathology. More than 97% of the senescent cells were excitatory neurons and overlapped with tau-containing neurofibrillary tangles (NFTs). Cyclin dependent kinase inhibitor 2D ( CDKN2D/ p19) was predicted as the most significant contributor to the primary senescence eigengene. RNAscope and immunofluorescence confirmed its elevated expression in AD brain tissue whereby p19-expressing neurons had 1.8-fold larger nuclei and significantly more cells with lipofuscin than p19-negative neurons. These hallmark senescence phenotypes were further elevated in the presence of NFTs. Collectively, CDKN2D/ p19-expressing neurons with NFTs represent a unique cellular population in human AD with a senescence phenotype. The eigengenes developed may be useful in future senescence profiling studies as they accurately identified senescent cells in snRNASeq datasets and predicted biomarkers for histological investigation.
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APA 7th
Dehkordi, S. K., Walker, J., Sah, E., Bennett, E., Atrian, F., Frost, B., et al. (2021). Profiling senescent cells in human brains reveals neurons with CDKN2D/p19 and tau neuropathology. Nature aging. https://doi.org/10.1038/s43587-021-00142-3
Vancouver
Dehkordi SK, Walker J, Sah E, Bennett E, Atrian F, Frost B, et al. Profiling senescent cells in human brains reveals neurons with CDKN2D/p19 and tau neuropathology. Nature aging. 2021. doi:10.1038/s43587-021-00142-3. PMID: 35531351.
BibTeX
@article{dehkordi2021-35531351,
author = {Dehkordi, S. K. and Walker, J. and Sah, E. and Bennett, E. and Atrian, F. and Frost, B. and Woost, B. and Bennett, R. E. and others},
title = {{Profiling senescent cells in human brains reveals neurons with CDKN2D/p19 and tau neuropathology}},
journal = {Nature aging},
year = {2021},
doi = {10.1038/s43587-021-00142-3},
pmid = {35531351},
url = {https://doi.org/10.1038/s43587-021-00142-3}
}
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Key findings
- Cyclin dependent kinase inhibitor 2D ( CDKN2D/ p19) was predicted as the most significant contributor to the primary senescence eigengene.
- RNAscope and immunofluorescence confirmed its elevated expression in AD brain tissue whereby p19-expressing neurons had 1.8-fold larger nuclei and significantly more cells with lipofuscin than p19-negative neurons.
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Study details
- Evidence strengthLow
How this study scored 43/100
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 25 of the 58 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature aging) |
| 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 35531351) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 25 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 25 of the 58 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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