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| Status |
Public on Dec 31, 2022 |
| Title |
Reduced LYNX1 and epilepsy phenotype-related changes in transcriptome of human iPSC-derived neural progenitors modeling fragile X syndrome |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Transcriptome analysis of RNA samples collected from human control and FXS iPS cell-derived neural progenitors at day 1 and day 7 of differentiation
Lack of fragile X mental retardation protein results in fragile X syndrome (FXS), which is the most common inherited intellectual disability syndrome and serves as an excellent model disease to study molecular mechanisms behind neuropsychiatric comorbidities. We compared the transcriptomes of human neural progenitors (NPCs) generated from patient-derived induced pluripotent stem cells (iPSCs) of three FXS and three control male donors. Altered expression of RAD51C, PPIL3, GUCY1A2, MYD88, TRAPPC4, LYNX1, and GTF2A1L in FXS NPCs suggested changes related to triplet repeat instability, RNA splicing, testes development, and pathways previously shown to be affected in FXS. LYNX1 is a cholinergic break of tissue plasminogen activator (tPA)-dependent plasticity, and its reduced expression was consistent with augmented tPA-dependent radial glial process growth in NPCs derived from FXS iPSC lines. An analysis of gene expression in LYNX1-related signaling pathways revealed that NPCs derived from an FXS male with concomitant epilepsy differed from the other FXS NPCs. The differently expressed genes comprised several epilepsy-related genes, including genes shown to cause the auditory epilepsy phenotype in the murine model of FXS. Functional enrichment analysis highlighted regulation of insulin-like growth factor pathway in human NPCs modeling FXS with epilepsy. Our results link early gene expression changes of FXS NPCs with the pathogenesis of FXS and comorbid epilepsy.
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| Overall design |
In this study, we analyzed gene expression profile of human iPS cell-derived neural progenitors reprogrammed from somatic cells of 3 healthy subjects and 3 patients diagnosed with FXS using the Affymetrix ClariomTM D Human array.
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| Contributor(s) |
Talvio K, Minkeviciene R, Corcoran P, Castrén M |
| Citation(s) |
36506088 |
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| Submission date |
Oct 30, 2022 |
| Last update date |
Jan 04, 2023 |
| Contact name |
Maija Castrén |
| E-mail(s) |
[email protected]
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| Organization name |
University of Helsinki
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| Department |
Faculty of Medicine/Physiology
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| Street address |
P.O.BOX 63
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| City |
Helsinki |
| ZIP/Postal code |
00014 |
| Country |
Finland |
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| Platforms (1) |
| GPL23126 |
[Clariom_D_Human] Affymetrix Human Clariom D Assay [transcript (gene) version] |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA895912 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE216875_RAW.tar |
420.9 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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