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| Status |
Public on Mar 03, 2020 |
| Title |
Human iPSC-derived neurons and cerebral organoids establish differential effects of germline NF1 gene mutations |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Neurofibromatosis type 1 (NF1) is a common neurodevelopmental disorder caused by a spectrum of distinct germline NF1 gene mutations, traditionally viewed as equivalent loss-of-function alleles. To specifically address the issue of mutational equivalency in a disease with considerable clinical heterogeneity, we engineered seven isogenic human induced pluripotent stem cell lines, each with a different NF1 patient NF1 mutation, to identify potential NF1 mutation-specific effects on human central nervous system cells and tissues. While all mutations increased proliferation and RAS activity in two-dimensional (2D) neural progenitor cells (NPCs) and astrocytes, we observed striking NF1 mutation-specific effects on 2D NPC dopamine levels and NPC proliferation, apoptosis, and neuronal differentiation in developing cerebral organoids. Together, these findings demonstrate NF1 mutational specificity at the cellular and tissue levels, suggesting that the germline NF1 gene mutation is one factor that underlies clinical variability.
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| Overall design |
Analyze differential clustering of gene expression between patient-derived and isogenic NPCs harboring two separate NF1 mutations (1185+1G>A; 6513T>A) or no NF1 mutation (control; CTL)
nf1 = NF1 mutation 1185+1G>A
nf8 = NF1 mutation 6513T>A
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| Contributor(s) |
Anastasaki C, Wegscheid ML, Hartigan K, Papke JB, Kopp ND, Chen J, Dougherty JD, Cobb O, Gutmann DH |
| Citation(s) |
32243842 |
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| Submission date |
Jan 31, 2020 |
| Last update date |
Apr 27, 2020 |
| Contact name |
David Gutmann |
| Organization name |
Washington University in St Louis
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| Department |
Neurology
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| Lab |
NF Center
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| Street address |
660 S Euclid Ave
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| City |
St Louis |
| State/province |
MO |
| ZIP/Postal code |
63110 |
| Country |
USA |
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| Platforms (1) |
| GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA604182 |
| SRA |
SRP246325 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE144601_DEG_gene_list.txt.gz |
2.2 Mb |
(ftp)(http) |
TXT |
| GSE144601_Normalized_gene_counts.txt.gz |
1.6 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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