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| Status |
Public on Apr 27, 2016 |
| Title |
Musashi-2 attenuates AHR signalling to expand human haematopoietic stem cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
A greater understanding of the molecular pathways that underpin the unique human hematopoietic stem and progenitor cell (HSPC) self-renewal program will improve strategies to expand these critical cell types for regenerative therapies. The post-transcriptional mechanisms guiding HSPC fate during ex vivo expansion have not been closely investigated. Using shRNA-mediated knockdown, we show that the RNA-binding protein (RBP) Musashi-2 (MSI2) is required for human HSPC self-renewal. Conversely, when overexpressed, MSI2 induces multiple pro-self-renewal phenotypes, including significant ex vivo expansion of short- and long-term repopulating cells through direct attenuation of aryl hydrocarbon receptor (AHR) signaling. Using a global analysis of MSI2-RNA interactions, we determined that MSI2 post-transcriptionally downregulates canonical AHR pathway components in cord blood HSPCs. Our study provides new mechanistic insight into RBP-controlled RNA networks that underlie the self-renewal process and provides evidence that manipulating such networks can provide a novel means to enhance the regenerative potential of human HSPCs expanded ex vivo.
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| Overall design |
4 samples were used for RNA-seq (4 biological duplicate) including 2 sets of control samples (irrelvant shRNA kncok-downs)
|
| Web link |
http://www.nature.com/nature/journal/v532/n7600/full/nature17665.html
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| |
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| Contributor(s) |
Wilhelm BT, Hope K, Rentas S, Holzapfel N, Belew MS, Pratt G, Bader G, Voisin V, Yeo G |
| Citation(s) |
27121842 |
| |
| Submission date |
Jul 09, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Brian Wilhelm |
| E-mail(s) |
[email protected]
|
| Organization name |
University of Montreal
|
| Street address |
2950 Chemin Polytechnique
|
| City |
Montreal |
| ZIP/Postal code |
H1J 3R4 |
| Country |
Canada |
| |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (8)
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|
| Relations |
| BioProject |
PRJNA289354 |
| SRA |
SRP060605 |
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