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| Status |
Public on Nov 30, 2012 |
| Title |
Attenuation of miR-126 activity expands HSC in vivo without exhaustion |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Life-long blood cell production is governed through the poorly understood integration of cell-intrinsic and -extrinsic control of hematopoietic stem cell (HSC) quiescence and activation. MicroRNAs (miRNAs) coordinately regulate multiple targets within signaling networks making them attractive candidate HSC regulators. We report that miR-126, a miRNA expressed in HSC and early progenitors, plays a pivotal role in restraining cell cycle progression of HSC in vitro and in vivo. miR-126 knockdown using lentiviral sponges increased HSC proliferation without inducing exhaustion, resulting in expansion of mouse and human long-term repopulating HSC. Conversely, enforced miR-126 expression impaired cell cycle entry leading to progressively reduced hematopoietic contribution. In HSC/early progenitors, miR-126 regulates multiple targets within the PI3K/AKT/GSK3β pathway thus attenuating signal transduction in response to extrinsic signals. These data establish that miR-126 sets a threshold for HSC activation and thus governs HSC pool size, demonstrating the importance of miRNA in the control of HSC function.
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| Overall design |
Total RNA was extracted from cord blood Lin- cells and treated with mir126 shRNA or mir126 containing viral particles (and corresponding controls)
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| Contributor(s) |
Lechman ER, van Galen P, Dick JE, Voisin V, Bader GD |
| Citation(s) |
23142521 |
| Submission date |
Aug 29, 2012 |
| Last update date |
Aug 13, 2018 |
| Contact name |
John E Dick |
| Organization name |
Ontario Cancer Institute
|
| Street address |
101 College St. Toronto
|
| City |
Toronto |
| ZIP/Postal code |
M5G2C1 |
| Country |
Canada |
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| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA174082 |
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