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| Status |
Public on Apr 24, 2023 |
| Title |
Aberrant cortical layer development of brain organoids developed from Noonan syndrome-iPSCs |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Noonan syndrome (NS) is a genetic disorder mainly caused by gain-of-function mutations of SHP2. Although diverse neurological manifestations are commonly diagnosed in NS patients, mechanisms on how the SHP2 mutation induces the neurodevelopmental defects remain elusive. Here, we report that cortical organoids (NS-COs) derived from NS-induced pluripotent stem cells (iPSCs) exhibit developmental abnormalities, especially in excitatory neurons (ENs). Although NS-COs normally develop in appearance, single-cell transcriptomic analysis represented increment of EN population and overexpression of cortical layer markers in NS-COs. Surprisingly, EN subpopulation co-expressing upper layer marker SATB2 and deep layer maker CTIP2 was enriched in NS-COs during the cortical development. In parallel with the developmental disruptions, NS-COs also exhibited reduced synaptic connectivity. Collectively, our findings suggest that perturbed cortical layer identity and impeded neuronal connectivity account for the neurological manifestations of NS.
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| Overall design |
COs were obtained at week 8, 16, and 24 during the differentiation of WT-iPSCs, NS-iPSCs, and gene-corrected isogenic control cell line of NS-iPSCs (NS-Cor-iPSCs)
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| Web link |
https://doi.org/10.3390/ijms232213861
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| Contributor(s) |
Kim B, Koh Y, Park J, Han Y |
| Citation(s) |
36430334 |
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| Submission date |
Sep 20, 2022 |
| Last update date |
Apr 24, 2023 |
| Contact name |
Jong-Eun Park |
| Organization name |
Korea Advanced Institute of Science and Technology
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| Street address |
291, Daehak-ro, Yuseong-gu
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| City |
Daejeon |
| ZIP/Postal code |
34141 |
| Country |
South Korea |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (9)
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| GSM6594441 |
wk16-Cor, replicate 1, scRNAseq |
| GSM6594442 |
wk16-NS, replicate 1, scRNAseq |
| GSM6594443 |
wk16-WT, replicate 1, scRNAseq |
| GSM6594444 |
wk24-Cor, replicate 1, scRNAseq |
| GSM6594445 |
wk24-NS, replicate 1, scRNAseq |
| GSM6594446 |
wk24-WT, replicate 1, scRNAseq |
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| Relations |
| BioProject |
PRJNA882459 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE213798_excitatory.rds.gz |
527.4 Mb |
(ftp)(http) |
RDS |
| GSE213798_total.rds.gz |
1.1 Gb |
(ftp)(http) |
RDS |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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