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| Status |
Public on Dec 15, 2011 |
| Title |
Expression profiles of HSPCs overexpressing microRNA cluster 99b/let-7e/125a, miR-125a, miR-155 and empty vector. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Hematopoietic stem/progenitor cell (HSPC) traits differ between genetically distinct mouse strains. For example, DBA/2 mice have a higher HSPC frequency compared to C57BL/6 mice. We performed a genetic screen for microRNAs that are differentially expressed between LSK, LS−K+, erythroid and myeloid cells isolated from C57BL/6 and DBA/2 mice. This analysis identified 131 microRNAs that were differentially expressed between cell types and 15 that were differentially expressed between mouse strains. Of special interest was an evolutionary conserved miR-cluster located on chromosome 17 consisting of miR-99b, let-7e and miR-125a. All cluster members were most highly expressed in LSKs and down-regulated upon differentiation. In addition, these microRNAs were higher expressed in DBA/2 cells compared to C57BL/6 cells, and thus correlated with HSPC frequency. To functionally characterize these microRNAs, we overexpressed the entire miR-cluster 99b/let-7e/125a and miR-125a alone in BM cells from C57BL/6 mice. Overexpression of the miR-cluster or miR-125a dramatically increased day-35 CAFC activity and caused severe hematopoietic phenotypes upon transplantation. We showed that a single member of the miR-cluster, namely miR-125a, is responsible for the majority of the observed miR-cluster overexpression effects. Finally, we performed genome-wide gene expression arrays and identified candidate target genes through which miR-125a may modulate HSPC fate.
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| Overall design |
These data consist of total mRNA obtained from 7-day cultured post 5-FU BM cells positively transduced with empty vector, miR-cluster 99b/let-7e/125a, miR-125a or miR-155 retroviral vector. Dataset (A) and dataset (B) were analyzed individualy. In each dataset, all samples were analyzed in independent biological triplicates.
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| Contributor(s) |
Gerrits A, Walasek MA, Olthof S, Weersing E, Ritsema M, Zwart E, van Os R, Bystrykh LV, de Haan G |
| Citation(s) |
22123844 |
| |
| Submission date |
Nov 14, 2011 |
| Last update date |
Jan 16, 2019 |
| Contact name |
Leonid Bystrykh |
| E-mail(s) |
[email protected]
|
| Organization name |
University Medical Center Groningen
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| Department |
European Research Institute for the Biology of Ageing - ERIBA
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| Lab |
Ageing Biology and Stem Cells
|
| Street address |
A. Deusinglaan 1
|
| City |
Groningen |
| State/province |
Groningen |
| ZIP/Postal code |
9713 AV |
| Country |
Netherlands |
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| Platforms (1) |
| GPL6887 |
Illumina MouseWG-6 v2.0 expression beadchip |
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| Samples (17)
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| This SubSeries is part of SuperSeries: |
| GSE33691 |
Genetic Screen Identifies MicroRNA Cluster 99b/let-7e/125a as a Regulator of Primitive Hematopoietic Cells |
|
| Relations |
| BioProject |
PRJNA154197 |
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