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Modeling Down syndrome neurodevelopment with isogenic cerebral organoids
Czerminski JT, King OD, Lawrence JB.. bioRxiv, 2022-05-26
Topic: Brain proteins, microglia and lab models
As a model of early fetal brain development in Down syndrome, this study examines cortical organoids generated from isogenic trisomic and disomic iPSC lines. Initially pools of organoids from a trisomic versus disomic line found broad transcriptomic differences and modest differences in cell-type representation, suggesting a potential neurodevelopmental phenotype due to Trisomy 21. To better control for multiple sources of variation, we undertook a very robust study of ~1,200 organoids, using an expanded panel of six isogenic subclones (three disomic and three trisomic).
Key findings
- Initially pools of organoids from a trisomic versus disomic line found broad transcriptomic differences and modest differences in cell-type representation, suggesting a potential neurodevelopmental phenotype due to Trisomy 21.
- To better control for multiple sources of variation, we undertook a very robust study of ~1,200 organoids, using an expanded panel of six isogenic subclones (three disomic and three trisomic).
- The power of the experimental design was indicated by exceptionally strong detection of the ~1.5-fold difference in most chr21 genes.
- Despite some variability in secreted Aβ-40 levels between “identical” cell lines, this Alzheimer-related phenotype was detected as clearly correlated with Trisomy 21.
Why it matters
This study used isogenic cerebral organoids to model early fetal brain development in Down syndrome and found broad differences in gene activity. It is a laboratory model of neurodevelopment and does not test any treatment, cure or prevention for Alzheimer's disease.
Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 18 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it. We have no data on impact for its field and year, so that was left out: it earned 17 of the 94 points we could judge it on, which is 18 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (bioRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| 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 “organoids”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 2 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.3 citations a year over 6 year(s) since 2022 |
| 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 | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Jeanne Bentley Lawrence: h-index 66 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Massachusetts Chan Medical School: institution h-index 990 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 17 / 94 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 17 of the 94 points we could judge it on is 18 out of 100. |
| Total | 18 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1101/2022.05.25.493459
- Original source →
- Free full text: bioRxiv (Cold Spring Harbor Laboratory) →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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. Check the citation against the original before you use it.
APA 7th
Czerminski, J. T., King, O. D., & Lawrence, J. B. (2022). Modeling Down syndrome neurodevelopment with isogenic cerebral organoids. bioRxiv. https://doi.org/10.1101/2022.05.25.493459
Vancouver
Czerminski JT, King OD, Lawrence JB. Modeling Down syndrome neurodevelopment with isogenic cerebral organoids. bioRxiv. 2022. doi:10.1101/2022.05.25.493459.
BibTeX
@article{czerminski2022-be7d48c0,
author = {Czerminski, J. T. and King, O. D. and Lawrence, J. B.},
title = {{Modeling Down syndrome neurodevelopment with isogenic cerebral organoids}},
journal = {bioRxiv},
year = {2022},
doi = {10.1101/2022.05.25.493459},
url = {https://doi.org/10.1101/2022.05.25.493459}
}
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