 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Apr 19, 2021 |
| Title |
HTA2.0 (human transcriptome array) analysis of control iPSC-derived motor neurons (MN), FUS-H517D-hetero-iPSC-MN, and FUS-H517D-homo-iPSC-MNs |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
To assess RNA regulation in the MN possessing mutated FUS-H517D gene.
Fused in sarcoma/translated in liposarcoma (FUS) is a causative gene of familial amyotrophic lateral sclerosis (fALS). Mutated FUS causes accumulation of DNA damage stress and stress granule (SG) formation, etc., thereby motor neuron (MN) death. However, key molecular etiology of mutated FUS-dependent fALS (fALS-FUS) remains unclear. Here, Bayesian gene regulatory networks (GRN) calculated by Super-Computer with transcriptome data sets of induced pluripotent stem cell (iPSC)-derived MNs possessing mutated FUSH517D (FUSH517D MNs) and FUSWT identified TIMELESS, PRKDC and miR-125b-5p as "hub genes" which influence fALS-FUS GRNs. miR-125b-5p expression up-regulated in FUSH517D MNs, showed opposite correlations against FUS and TIMELESS mRNA levels as well as reported targets of miR-125b-5p. In addition, ectopic introduction of miR-125b-5p could suppress mRNA expression levels of FUS and TIMELESS in the cells. Furthermore, we found TIMELESS and PRKDC among key players of DNA damage stress response (DDR) were down-regulated in FUSH517D MNs and cellular model analysis validated DDR under impaired DNA-PK activity promoted cytosolic FUS mis-localization to SGs. Our GRNs based on iPSC models would reflect fALS-FUS molecular etiology.
|
| |
|
| Overall design |
RNA from each control MN, FALS-derived MN possessing H517D mutation in hetero and isogenic MN possessing H517D mutation in homo. One array per biological replicate.
|
| |
|
| Contributor(s) |
Ishikawa M, Nogami M, Yano M, Okano H |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Aug 09, 2018 |
| Last update date |
Apr 21, 2021 |
| Contact name |
MASAHIRO NOGAMI |
| E-mail(s) |
masahiro.nogami@takeda.com
|
| Organization name |
Takeda Pharmaceutical Company Limited
|
| Department |
Research
|
| Lab |
Innovative Biology Labs
|
| Street address |
26-1, Muraoka-Higashi 2-Chome
|
| City |
Fujisawa |
| State/province |
Kanagawa |
| ZIP/Postal code |
251-8555 |
| Country |
Japan |
| |
|
| Platforms (1) |
| GPL17586 |
[HTA-2_0] Affymetrix Human Transcriptome Array 2.0 [transcript (gene) version] |
|
| Samples (60)
|
| GSM3325490 |
Control iPSC 201B7, 2wks, biological rep1 |
| GSM3325491 |
Control iPSC 201B7, 2wks, biological rep2 |
| GSM3325492 |
Control iPSC 201B7, 2wks, biological rep3 |
| GSM3325493 |
Control iPSC 409B2, 2wks, biological rep1 |
| GSM3325494 |
Control iPSC 409B2, 2wks, biological rep2 |
| GSM3325495 |
Control iPSC 409B2, 2wks, biological rep3 |
| GSM3325496 |
Control iPSC EKA03, 2wks, biological rep1 |
| GSM3325497 |
Control iPSC EKA03, 2wks, biological rep2 |
| GSM3325498 |
Control iPSC EKA03, 2wks, biological rep3 |
| GSM3325499 |
fALS-e46, 2wks, biological rep1 |
| GSM3325500 |
fALS-e46, 2wks, biological rep2 |
| GSM3325501 |
fALS-e46, 2wks, biological rep3 |
| GSM3325502 |
fALS-e48, 2wks, biological rep1 |
| GSM3325503 |
fALS-e48, 2wks, biological rep2 |
| GSM3325504 |
fALS-e48, 2wks, biological rep3 |
| GSM3325505 |
fALS-e54, 2wks, biological rep1 |
| GSM3325506 |
fALS-e54, 2wks, biological rep2 |
| GSM3325507 |
fALS-e54, 2wks, biological rep3 |
| GSM3325508 |
fALS-2e3, 2wks, biological rep1 |
| GSM3325509 |
fALS-2e3, 2wks, biological rep2 |
| GSM3325510 |
fALS-2e3, 2wks, biological rep3 |
| GSM3325511 |
genome-edited iPSC 409B2-Ho1, 2wks, biological rep1 |
| GSM3325512 |
genome-edited iPSC 409B2-Ho1, 2wks, biological rep2 |
| GSM3325513 |
genome-edited iPSC 409B2-Ho1, 2wks, biological rep3 |
| GSM3325514 |
genome-edited iPSC 409B2-Ho2, 2wks, biological rep1 |
| GSM3325515 |
genome-edited iPSC 409B2-Ho2, 2wks, biological rep2 |
| GSM3325516 |
genome-edited iPSC 409B2-Ho2, 2wks, biological rep3 |
| GSM3325517 |
genome-edited iPSC 409B2-Ho3, 2wks, biological rep1 |
| GSM3325518 |
genome-edited iPSC 409B2-Ho3, 2wks, biological rep2 |
| GSM3325519 |
genome-edited iPSC 409B2-Ho3, 2wks, biological rep3 |
| GSM3325520 |
Control iPSC 201B7, 4wks, biological rep1 |
| GSM3325521 |
Control iPSC 201B7, 4wks, biological rep2 |
| GSM3325522 |
Control iPSC 201B7, 4wks, biological rep3 |
| GSM3325523 |
Control iPSC 409B2, 4wks, biological rep1 |
| GSM3325524 |
Control iPSC 409B2, 4wks, biological rep2 |
| GSM3325525 |
Control iPSC 409B2, 4wks, biological rep3 |
| GSM3325526 |
Control iPSC EKA03, 4wks, biological rep1 |
| GSM3325527 |
Control iPSC EKA03, 4wks, biological rep2 |
| GSM3325528 |
Control iPSC EKA03, 4wks, biological rep3 |
| GSM3325529 |
fALS-e46, 4wks, biological rep1 |
| GSM3325530 |
fALS-e46, 4wks, biological rep2 |
| GSM3325531 |
fALS-e46, 4wks, biological rep3 |
| GSM3325532 |
fALS-e48, 4wks, biological rep1 |
| GSM3325533 |
fALS-e48, 4wks, biological rep2 |
| GSM3325534 |
fALS-e48, 4wks, biological rep3 |
| GSM3325535 |
fALS-e54, 4wks, biological rep1 |
| GSM3325536 |
fALS-e54, 4wks, biological rep2 |
| GSM3325537 |
fALS-e54, 4wks, biological rep3 |
| GSM3325538 |
fALS-2e3, 4wks, biological rep1 |
| GSM3325539 |
fALS-2e3, 4wks, biological rep2 |
| GSM3325540 |
fALS-2e3, 4wks, biological rep3 |
| GSM3325541 |
genome-edited iPSC 409B2-Ho1, 4wks, biological rep1 |
| GSM3325542 |
genome-edited iPSC 409B2-Ho1, 4wks, biological rep2 |
| GSM3325543 |
genome-edited iPSC 409B2-Ho1, 4wks, biological rep3 |
| GSM3325544 |
genome-edited iPSC 409B2-Ho2, 4wks, biological rep1 |
| GSM3325545 |
genome-edited iPSC 409B2-Ho2, 4wks, biological rep2 |
| GSM3325546 |
genome-edited iPSC 409B2-Ho2, 4wks, biological rep3 |
| GSM3325547 |
genome-edited iPSC 409B2-Ho3, 4wks, biological rep1 |
| GSM3325548 |
genome-edited iPSC 409B2-Ho3, 4wks, biological rep2 |
| GSM3325549 |
genome-edited iPSC 409B2-Ho3, 4wks, biological rep3 |
|
| Relations |
| BioProject |
PRJNA485257 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE118336_RAW.tar |
1.5 Gb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
|
|
|
|
 |
Less...
More...