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Single-cell protein activity analysis identifies recurrence-associated renal tumor macrophages
Obradovic A, Chowdhury N, Haake SM, Ager C, Wang V, Vlahos L, Guo XV, Aggen DH et al.. Cell, 2021-05-20
Topic: Brain proteins, microglia and lab models
Clear cell renal carcinoma (ccRCC) is a heterogeneous disease with a variable post-surgical course. To assemble a comprehensive ccRCC tumor microenvironment (TME) atlas, we performed single-cell RNA sequencing (scRNA-seq) of hematopoietic and non-hematopoietic subpopulations from tumor and tumor-adjacent tissue of treatment-naive ccRCC resections. We leveraged the VIPER algorithm to quantitate single-cell protein activity and validated this approach by comparison to flow cytometry.
Key findings
- To assemble a comprehensive ccRCC tumor microenvironment (TME) atlas, we performed single-cell RNA sequencing (scRNA-seq) of hematopoietic and non-hematopoietic subpopulations from tumor and tumor-adjacent tissue of treatment-naive ccRCC resections.
- We leveraged the VIPER algorithm to quantitate single-cell protein activity and validated this approach by comparison to flow cytometry.
- The analysis identified key TME subpopulations, as well as their master regulators and candidate cell-cell interactions, revealing clinically relevant populations, undetectable by gene-expression analysis.
- Specifically, we uncovered a tumor-specific macrophage subpopulation characterized by upregulation of TREM2/APOE/C1Q, validated by spatially resolved, quantitative multispectral immunofluorescence.
Why it matters
This study analyzed macrophages in kidney cancer, not Alzheimer's disease. It provides no information about treating, curing, or preventing Alzheimer's disease.
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Study details
- Evidence strengthModerate
How this study scored 59/100
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 (Cell) |
| Journal's citation record | 4 / 4 | Cell: journal h-index 1,220 (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 | 3 / 5 | Rated “moderate” 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 | 6 / 7 | Cited 352 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 50.3 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 5 / 6 | Cited 36.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 4 / 4 | Cited 206 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Charles G. Drake: h-index 112 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Johns Hopkins University: institution h-index 2,306 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34019793) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 59 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Obradovic, A., Chowdhury, N., Haake, S. M., Ager, C., Wang, V., Vlahos, L., et al. (2021). Single-cell protein activity analysis identifies recurrence-associated renal tumor macrophages. Cell. https://doi.org/10.1016/j.cell.2021.04.038
Vancouver
Obradovic A, Chowdhury N, Haake SM, Ager C, Wang V, Vlahos L, et al. Single-cell protein activity analysis identifies recurrence-associated renal tumor macrophages. Cell. 2021. doi:10.1016/j.cell.2021.04.038. PMID: 34019793.
BibTeX
@article{obradovic2021-34019793,
author = {Obradovic, A. and Chowdhury, N. and Haake, S. M. and Ager, C. and Wang, V. and Vlahos, L. and Guo, X. V. and Aggen, D. H. and others},
title = {{Single-cell protein activity analysis identifies recurrence-associated renal tumor macrophages}},
journal = {Cell},
year = {2021},
doi = {10.1016/j.cell.2021.04.038},
pmid = {34019793},
url = {https://doi.org/10.1016/j.cell.2021.04.038}
}
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