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Series GSE144601 Query DataSets for GSE144601
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
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.
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
Contributor(s) Anastasaki C, Wegscheid ML, Hartigan K, Papke JB, Kopp ND, Chen J, Dougherty JD, Cobb O, Gutmann DH
Citation(s) 32243842
Submission date Jan 31, 2020
Last update date Apr 27, 2020
Contact name David Gutmann
Organization name Washington University in St Louis
Department Neurology
Lab NF Center
Street address 660 S Euclid Ave
City St Louis
State/province MO
ZIP/Postal code 63110
Country USA
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (12)
GSM4291766 ctl-1
GSM4291767 ctl-2
GSM4291768 ctl-3
BioProject PRJNA604182
SRA SRP246325

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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
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