 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jul 01, 2014 |
| Title |
Targeted correction of RUNX1 mutation in FPD patient-specific induced pluripotent stem cells rescues megakaryopoietic defects |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML) is an autosomal dominant disease of the hematopoietic system, which is caused by heterozygous mutations in RUNX1. FPD/AML patients have a bleeding disorder characterized by thrombocytopenia with reduced platelet numbers and functions, and a tendency to develop AML. Currently no suitable animal models exist for FPD/AML as Runx1+/- mice and zebrafish do not develop bleeding disorders or leukemia. Here we derived induced pluripotent stem cells (iPSCs) from two patients in a family with FPD/AML, and found that the FPD iPSCs display defects in megakaryocytic differentiation in vitro. We corrected the RUNX1 mutation in one FPD iPSC line through gene targeting, which led to normalization of megakaryopoiesis of the iPSCs in culture. Our results demonstrate successful in vitro modeling of FPD with patient-specific iPSCs and confirm that RUNX1 mutations are responsible for megakaryopoietic defects in FPD patients.
|
| |
|
| Overall design |
Here, we derived iPSCs from two FPD/AML patients and demonstrated that these iPSCs have a megakaryopoietic defect in culture. Importantly we were able to rescue the megakaryopoietic defect by correcting the RUNX1 mutation with a gene targeting strategy enhanced by zinc finger nucleases (ZFNs). Three independent samples were obtained for each time point.
|
| |
|
| Contributor(s) |
Kwon EM, Elkahloun AG, Liu PP, Wu W |
| Citation(s) |
25114263 |
| |
| Submission date |
Jan 22, 2014 |
| Last update date |
Mar 15, 2019 |
| Contact name |
abdel G Elkahloun |
| E-mail(s) |
abdel@mail.nih.gov
|
| Phone |
301 402 3170
|
| Organization name |
NHGRI-NIH
|
| Lab |
MICROARRAY CORE
|
| Street address |
50, SOUTH DRIVE
|
| City |
BETHESDA |
| ZIP/Postal code |
20892 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL16686 |
[HuGene-2_0-st] Affymetrix Human Gene 2.0 ST Array [transcript (gene) version] |
|
| Samples (9)
|
| GSM1312309 |
RUNX1 corrected clone E, Biological replicate 1 |
| GSM1312310 |
RUNX1 corrected clone E, Biological replicate 2 |
| GSM1312311 |
RUNX1 corrected clone E, Biological replicate 3 |
| GSM1312312 |
RUNX1 corrected clone F, Biological replicate 1 |
| GSM1312313 |
RUNX1 corrected clone F, Biological replicate 2 |
| GSM1312314 |
RUNX1 corrected clone F, Biological replicate 3 |
|
| Relations |
| BioProject |
PRJNA236116 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE54295_RAW.tar |
82.2 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
|
|
|
|
 |
Less...
More...