Altered cell and RNA isoform diversity in aging Down syndrome brains
Carter R Palmer, Christine S Liu, William J Romanow, Ming-Hsiang Lee, Jerold Chun. Proceedings of the National Academy of Sciences of the United States of America, 2021-11-23
Topic: Genetics and APOE
Down syndrome (DS), trisomy of human chromosome 21 (HSA21), is characterized by lifelong cognitive impairments and the development of the neuropathological hallmarks of Alzheimer's disease (AD). The cellular and molecular modifications responsible for these effects are not understood. Here we performed single-nucleus RNA sequencing (snRNA-seq) employing both short- (Illumina) and long-read (Pacific Biosciences) sequencing technologies on a total of 29 DS and non-DS control prefrontal cortex samples. In DS, the ratio of inhibitory-to-excitatory neurons was significantly increased, which was not observed in previous reports examining sporadic AD. DS microglial transcriptomes displayed AD-related aging and activation signatures in advance of AD neuropathology, with increased microglial expression of C1q complement genes (associated with dendritic pruning) and the HSA21 transcription factor gene RUNX1 Long-read sequencing detected vast RNA isoform diversity within and among specific cell types, including numerous sequences that differed between DS and control brains. Notably, over 8,000 genes produced RNAs containing intra-exonic junctions, including amyloid precursor protein (APP) that had previously been associated with somatic gene recombination. These and related results illuminate large-scale cellular and transcriptomic alterations as features of the aging DS brain.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Palmer, C. R., Liu, C. S., Romanow, W. J., Lee, M.-H., & Chun, J. (2021). Altered cell and RNA isoform diversity in aging Down syndrome brains. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.2114326118
Vancouver
Palmer CR, Liu CS, Romanow WJ, Lee M.-H, Chun J. Altered cell and RNA isoform diversity in aging Down syndrome brains. Proceedings of the National Academy of Sciences of the United States of America. 2021. doi:10.1073/pnas.2114326118. PMID: 34795060.
BibTeX
@article{palmer2021-34795060,
author = {Palmer, Carter R and Liu, Christine S and Romanow, William J and Lee, Ming-Hsiang and Chun, Jerold},
title = {{Altered cell and RNA isoform diversity in aging Down syndrome brains}},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2021},
doi = {10.1073/pnas.2114326118},
pmid = {34795060},
url = {https://doi.org/10.1073/pnas.2114326118}
}
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Key findings
- In DS, the ratio of inhibitory-to-excitatory neurons was significantly increased, which was not observed in previous reports examining sporadic AD.
- DS microglial transcriptomes displayed AD-related aging and activation signatures in advance of AD neuropathology, with increased microglial expression of C1q complement genes (associated with dendritic pruning) and the HSA21 transcription factor gene RUNX1 Long-read sequencing detected vast RNA isoform diversity within and among specific cell types, including numerous sequences that differed between DS and control brains.
- Notably, over 8,000 genes produced RNAs containing intra-exonic junctions, including amyloid precursor protein (APP) that had previously been associated with somatic gene recombination.
- These and related results illuminate large-scale cellular and transcriptomic alterations as features of the aging DS brain.
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Study details
- Participants29
- Evidence strengthLow
How this study scored 48/100
Published in a peer-reviewed journal. Scored zero for study design, 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, multi-centre collaboration and free to read, so those were left out: it earned 27 of the 56 points we could judge it on, which is 48 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Proceedings of the National Academy of Sciences of the United States of America) |
| 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 | 1 / 4 | 29 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| 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 34795060) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 27 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 27 of the 56 points we could judge it on is 48 out of 100. |
| Total | 48 / 100 | — |
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