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| Status |
Public on Jun 20, 2017 |
| Title |
Microarray expression analysis of wild type and Erg knockdown bone marrow hematopoietic stem and progenitor cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Erg is an ETS family transcription factor frequently overexpressed in human leukemias and has been implicated as a key regulator of hematopoietic stem cells (HSCs). However how Erg controls normal hematopoiesis, particularly at the stem cell level, remains poorly understood. Using homologous recombination, we generated an Erg knockdown allele (Ergkd) in which Erg expression can be restored upon Cre-mediated excision of a Stopper cassette. In Ergkd/+ mice, ~40% reduction in Erg dosage perturbed both fetal liver and bone marrow hematopoiesis by reducing the numbers of Lin-Sca-1+c-Kit+ (LSK) hematopoietic stem and progenitor cells (HSPCs) and megakaryocytic progenitors.
By genetic mosaic analysis, we found Erg-restored HSPCs outcompeted Ergkd/+ HSPCs for contributing to adult hematopoiesis in vivo. Intriguingly, HSC differentiation also appeared attenuated, leading to accumulation of long-term HSCs in the mutant LSK population. Accordingly, microarray analysis of Erg-restored and Ergkd/+ HSPCs from the same animal revealed enrichment of stem cell-related pathways in Ergkd/+ HSPCs. Overall, reduced Erg dosage perturbs hematopoiesis by reducing HSC numbers and impairing HSC differentiation, possibly via two Erg targets, Jun and Myc.
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| Overall design |
Erg-restored (to wild type) YFP+ HSPCs and Erg-knockdown (~40% reduction) YFP- HSPCs were sorted from the same mouse [Mx1Cre;Ergkd/+;Rosa26-Stop-YFP (R26Y)]; RNA was prepared from the sorted HSPCs, amplified by Nugen V2 and applied to Affymetrix mouse genome 430 2.0 arrays.
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| Contributor(s) |
Koch ML, Li Z |
| Citation(s) |
28436588 |
| Submission date |
Jul 08, 2013 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Zhe Li |
| E-mail(s) |
zli4@rics.bwh.harvard.edu
|
| Organization name |
Brigham and Women's Hospital
|
| Department |
Medicine, Genetics Division
|
| Lab |
Li Lab
|
| Street address |
77 Avenue Louis Pasteur, Room 466
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA210779 |
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