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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Mar 14, 2014 |
| Title |
Oncogenic Nras has a bimodal effect on hematopoietic stem cells promoting proliferation and self-renewal |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Pre-leukemic mutations are thought to promote clonal expansion of hematopoietic stem cells (HSCs) by increasing self-renewal and competitiveness. However, mutations that increase HSC proliferation tend to reduce competitiveness and self-renewal potential, raising the question of how a mutant HSC can sustainably outcompete wild-type HSCs. Activating mutations in NRAS are prevalent in human myeloproliferative disease and leukemia. Here we show that a single allele of oncogenic NrasG12D increases HSC proliferation but also increases reconstituting and self-renewal potential upon serial transplantation in irradiated mice, all without immortalizing HSCs or causing leukemia in our experiments. NrasG12D also confers long-term self-renewal potential upon multipotent progenitors. To explore the mechanism by which NrasG12D promotes HSC proliferation and self-renewal we assessed HSC cell cycle kinetics using H2B-GFP label retention. We found that NrasG12D had a bimodal effect on HSCs, increasing the proliferation of some HSCs while increasing the quiescence and competitiveness of other HSCs. One signal can therefore increase HSC proliferation, competitiveness, and self-renewal through a bimodal effect that promotes proliferation in some HSCs and quiescence in others.
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| Overall design |
12 RNA samples from mouse bone marrows were analyzed. There are three biological replicates for each subtype.
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| Contributor(s) |
Li Q, Bohin N, Wen T, Magee J, Chen S, Shannon K, Morrison S |
| Citation(s) |
24284627 |
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| Submission date |
Mar 15, 2013 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Shann-Ching Chen |
| E-mail(s) |
Shann-Ching.Chen@stjude.org
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| Organization name |
St. Jude Children's Research Hospital
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| Department |
Pathology
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| Street address |
262 Danny Thomas Place
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| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38105 |
| Country |
USA |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA193193 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE45194_RAW.tar |
44.4 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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