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| Status |
Public on Jan 30, 2018 |
| Title |
A Forward Genetic Screen Targeting the Endothelium Reveals a Regulatory Role for the Lipid Kinase Pi4ka in Myelo- and Erythropoiesis [clonality] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Definitive hematopoietic cells arise from hemogenic endothelium during mid-gestation, indicating a direct link between blood and the endothelial-lined vessels. We sought to determine whether mutations initiated in the hemogenic endothelium would yield hematopoietic abnormalities or malignancies. Here we demonstrate that transposon mutagenesis targeting endothelial cells in mice promotes the development of hematopoietic pathologies that are both myeloid and lymphoid in nature. Sequencing of the disrupted genes identified several previously recognized candidate cancer drivers and furthermore revealed that mutations in the lipid kinase Pi4ka can result in myeloid and erythroid dysfunction. Subsequent validation experiments showed that targeted inactivation of the Pi4ka catalytic domain or reduction in mRNA expression inhibited myeloid and erythroid cell differentiation in vitro and promoted anemia in vivo through a mechanism that includes, but it is not limited to deregulation of Akt signaling. Finally, we provide evidence linking PI4KAP2, previously considered a “pseudogene”, with human myeloid and erythroid leukemia.
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| |
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| Overall design |
mRNA transcriptional comparison between two pieces of spleen from three SBxVEC-Cre+ animals and three control animals to assess clonality of each spleen as a whole.
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| |
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| Contributor(s) |
Ziyad S, Su T, Iruela-Arispe ML |
| Citation(s) |
29386109 |
| |
| Submission date |
Dec 20, 2017 |
| Last update date |
Aug 26, 2019 |
| Contact name |
Safiyyah Ziyad |
| E-mail(s) |
sziyad@ucla.edu
|
| Organization name |
University of California, Los Angeles
|
| Department |
Molecular, Cell and Developmental Biology
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| Lab |
Dr Luisa Iruela-Arispe
|
| Street address |
621 Charles E. Young Drive, South
|
| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
|
| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE108355 |
A Forward Genetic Screen Targeting the Endothelium Reveals a Regulatory Role for the Lipid Kinase Pi4ka in Myelo- and Erythropoiesis |
|
| Relations |
| BioProject |
PRJNA423253 |
| SRA |
SRP127255 |
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